April: CRPS/RSD Clinical Trials

Of interest:

Elsevier has launched a service called Patient Research BETA that may prove very useful to patients researching their own conditions or the treatments/diagnoses of loved ones. Access to the many wonderful journals and medical information services out there requires beaucoup bucks; This is a response to that situation. $4.95 is a low price to pay for research articles -- at least, it is the lowest I've ever seen.

From Elsevier: The [Patient Research] pilot will help the individual journals assess the level of demand for medical information from the public and provide a public service to those in medical need. The journals testing this approach cover different medical fields and represent both publisher and society journals. These journals are testing this approach because they have content that is relevant to common medical conditions and are relatively straightforward to understand.

This pilot approach allows individual journals to test, learn and adapt their approaches accordingly, based on facts and ensures that the effects of new approaches to distribution of our content are meeting a real need within the communities we serve.



After pledging to post a monthly update on clinical trials for CRPS/RSD, I sure have fallen short. My apologies. Sadly, there has not been a huge turnover in what is available since my last offering in September.

Pay close attention to study requirements -- sometimes involvement of certain limbs is specified, sometimes a distinction between CRPS Type 1 or 2, sometimes length of illness. Some studies require procedures, some offer treatments (blindly, since for research), some require that you not have experienced any prior treatment.

I have no information regarding remuneration.

Boy, that'd be the day, huh? Get CRPS and make millions participating in clinical trials... I'll put that on my list, right after making a living as a juror.

1 Autonomic Dysfunction and Spinal Cord Stimulation in Complex Regional Pain Syndrome

NOTE: Vanderbilt Univ. last verified this study in OCTOBER 2008. Since this is listed as a 24 month study, please check its status before getting too excited at the prospect of possibly receiving a SCS!

PURPOSE: To demonstrate that spinal cord stimulator [SCS] has an effect on sympathetic function (the one that give us the fight and flight response). Therefore, if the spinal cord stimulator has an effect on sympathetic function, the responses from CRPS patients to different stimuli will differ significantly pre and post SCS implant. If CRPS patients exhibit autonomic dysfunction, CRPS patients could be stratified according to their sympathetic function pre-implant. It is expected that patients with a moderate/mild form of autonomic dysfunction will have better outcomes with the SCS.

Currently the mechanisms of Complex Regional Pain Syndrome (CRPS) are poorly understood and stratification of either diagnosis or therapy is very weak. . There is a great need to develop and validate more objective methods to characterize and stratify CRPS that better diagnostic and therapeutic approaches are available. Spinal Cord Stimulation (SCS) has been used as the last resource to alleviate pain and re-establish function in CRPS patients. However, there is a disagreement over how it works. An underlying concept is that it works by modulating autonomic nervous system (ANS) activity. Therefore, ANS parameters could be useful to stratify patients. Our preliminary studies indicated that SCS has also an effect on blood pressure regulation and improves the CRPS patients' response to Valsalva maneuver -a test of autonomic function. The Autonomic Nervous System function in adult CRPS patients has not yet been studied. The only existing study of CRPS and autonomic function showed that 15% of the patients suffer from syncope and increased heart rate during upright position similar to same aged patients with postural tachycardia syndrome - a syndrome of autonomic dysfunction. It is unclear if autonomic dysfunction is present in CRPS patients because ANS activity is altered by chronic pain or whether or not ANS activity contributes to CRPS. Therefore, we proposed to study the autonomic function in CRPS patients by standardized autonomic function and to evaluate the effect of the SCS on autonomic function in CRPS patients before and after spinal cord stimulator implant. This is a 24 months study.

Inclusion Criteria:
CRPS patients meeting the inclusion criteria according to the International Association for the Study of Pain Task Force will be included in the study.
Age: 18 to 65.
Disease duration of at least 6 months.
History of unsuccessful long lasting therapies: physical therapy, transcutaneous electrical stimulation and medication.

Exclusion Criteria:
Presence of current or past pulmonary, hepatic, renal disease, arthritis, hematopoietic, and neurological diseases not related to CRPS.
Anticoagulant therapy, cardiac pacemaker used.
Pregnancy test for females is positive.

[I suggest, for background reading, this article:
Complex Regional Pain Syndrome: Manifestations and the Role of Neurostimulation in Its Management
Journal of Pain and Symptom Management, Volume 31, Issue 4, Pages S20-S24
M. Stanton-Hicks]

2 Effect of Delta-9-Tetrahydrocannabinol on the Prevention of Chronic Pain in Patients With Acute CRPS (ETIC-Study)

Sponsored by Ludwig-Maximilians - University of Munich

Again, this is listed as an open study, but then there's this:
Study Start Date -- September 2006
Estimated Study Completion Date -- December 2008

Recent animal data suggest that the endocannabinoid system is a promising target in the prevention of chronic pain. It has been shown that the endocannabinoid system modifies excitatory and inhibitory currents in structures involved in the development of chronic pain such as the amygdala.

CRPS is a neuropathic pain condition, which is known to become chronic in a significant percentage. The study compares the effect of low dose Delta9-Tetrahydrocannabinol (90 days) and placebo in acute CRPS. All patients will receive a standard treatment consisting of drug therapy and physiotherapy.

Primary Outcome Measures:
Incidence of chronic pain at one year assessed with Visual Analogue Scale (VAS)

Secondary Outcome Measures:
Changes in somatosensory phenotype at one year assessed with Quantitative Sensory Testing (QST)
Motor function of the affected extremity at one year assessed with a biometric evaluation
Changes in Health Related Quality of Life at one year assessed with SF-36
Changes in plasma endocannabinoid levels at 30, 60, 90 days and at one year

These articles may be of adjunct interest:

Cichewicz DL, Welch SP, Smith FL. Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal delta9- tetrahydrocannabinol. Eur J Pharmacol. 2005 Nov 21;525(1-3):74-82.

Cichewicz DL, McCarthy EA. Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther. 2003 Mar;304(3):1010-5.

Editorial on cannabinoids and chronic pain


3 Safety and Efficacy Study of Ethosuximide for the Treatment of Complex Regional Pain Syndrome (CRPS)

Study is at McGill (Montréal). "Pain remains the most debilitating symptom for adult patients suffering from complex regional pain syndrome (CRPS). Most CRPS patients gain little to no relief from current painkillers. The purpose of this study is to evaluate the efficacy and safety of ethosuximide in search of much-needed adjunctive therapy to relieve the pain and suffering associated with CRPS."

This is a single centre, parallel-group, double-blind, randomized, placebo-controlled pilot clinical trial for adults suffering from complex regional pain syndrome (CRPS).

Twelve (12) subjects diagnosed with CRPS will be enrolled and randomized to receive orally, either ethosuximide or placebo. If the maximum trial medication dosage (1500mg) is reached, the subject will be in the study for a maximum of 10 weeks from screening (Clinic Visit 1) to the end of the drug cessation period. The minimum period a subject could complete the study would be 4 weeks presuming they were not previously on any disallowed drugs and only found the 500mg dose tolerable.

4 Not yet recruiting Graded Exposure (GEXP) in Vivo Versus Physiotherapy in Complex Regional Pain Syndrome Type I (CRPS-I)

Study by Maastricht University Medical Center. "Research on the treatment of CRPS-I, as described in the Dutch evidence based treatment guidelines (Richtlijn Complex Regional Pain Syndrome type I, 2006), mainly showed improvement at the level of pain and coping with pain. Only little improvement in functional restoration was found. Research in other pain populations such al neck- and back-pain patients has shown that pain related fear contributes to the development of functional disability. GEXP in vivo which aims on systematically reducing fear of movement, shows promising results in CRPS-I patients (de Jong et al., 2005)."

The objective of the proposed project is to compare the effectivity of GEXP in vivo with that of standardized physiotherapy in CRPS-I patients with pain related fear.

The study population will consist of chronic CRPS-I patients between 18 and 65, with pain related fear (PHODA-LE-score ≥ 35 and PHODA-UE-score ≥ 32).

The two interventions that will be compared are GEXP in vivo (de Jong et al., 2005) and standardized physiotherapy according to the protocol of Oerlemans, Oostendorp, de Boo en Goris (1999). The GEXP in vivo comprises 17 sessions of one hour, the physiotherapy treatment of 34 sessions of 30 minutes. Both treatments will be given over a period of 17 weeks.

Inclusion Criteria:
Diagnosis CRPS-I according to IASP criteria.
Pain related (PHODA-LE-score ≥ 35 and PHODA-UE-score ≥ 32)
Age between 18 and 65.
Rehabilitation treatment has been indicated.

Exclusion Criteria:
Pregnancy.
Insufficient fluency in Dutch.
Generalized pain syndrome.
Dystonia.
Sympathectomy of the affected extremity.
Psychopathology
Involvement in a claim regarding the disease.
Substance abuse.
Symptoms on both upper or both lower extremities.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625976
Contact: Tim Gard, M.Sc. +31 43 3881594 T.Gard@dmkep.unimaas.nl
Contact: Marielle Goossens, Dr. +31 43 3881477 M.Goossens@dep.unimaas.nl

Additional Reading/Viewing:
Health Skills -- Reduction of pain-related fear in complex regional pain syndrome
Bethesda Physiocare: Physical Therapy Management of CRPS
eHow: How to Treat Complex Regional Pain Syndrome: Video Series

5 Double Blind Placebo Controlled Study of Outpatient Intravenous Ketamine for the Treatment of CRPS

Complex Regional Pain Syndrome is a debilitating and extremely difficult to treat condition. There is a large body of evidence demonstrating the therapeutic value of N-methyl-D-aspartate (NMDA)-receptor antagonists in CRPS. The NMDA antagonist ketamine has been shown to be effective in the treatment of CRPS, resulting in complete remission of the disease in some patients. The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS. A thorough evaluation of this procedure, providing information into the degree of relief and which of the constellation of RSD symptoms are best alleviated by this procedure would result in the optimization of this therapy for the treatment of CRPS.

Inclusion Criteria:
Patients diagnosed with CRPS based on the modified IASP (International Association for the Study of Pain) research criteria (Harden RN and Bruehl SP
Diagnostic Criteria: The Statistical Derivation of the Four Criterion Factors.
In CRPS: Current Diagnosis and Therapy, Progress in Pain Research and Management, Vol 32: pp 45-58, 2005), whose condition is intractable for at least six months and have failed at least three of the following therapies:

Nerve blocks
Opioid analgesics
Non-opioid analgesics
Non-steroidal anti-inflammatory drugs
Anti-seizure medications
Antidepressants
Muscle relaxants; or
Physical therapy.
The patients must be ketamine naïve and can be of either gender including all racial and minority groups. The patient's age must be between 18 and 65 years, inclusive.
The study subjects must report pain levels equal to or greater than 4 on a scale of 0-10 (0 = no pain and 10 = unbearable pain). The pain must be stable over time and not vary more that 1 pain level.
The patient must be on a stable dose of CRPS medications for 28 days prior to and throughout the duration of the study.
The patient must be accompanied by a responsible adult.
The patient will be instructed that he/she will not be allowed to drive home following the infusion. Therefore in order to be included in the study the subjects must arrange for transportation for the 10 day duration of the study.

Exclusion Criteria:
Patients less than 18 years of age will be excluded. In this initial study, patients over 65 years of age will be excluded due to possible unforeseen concomitant medical problem.
Patients that have previously undergone intravenous ketamine infusions will be excluded from the study.
Patients who are pregnant, are lactating, have known psychotic or psychiatric illness, are afflicted with glaucoma or have thyrotoxicosis will also be excluded.
Any patient that is unable to provide consent due to cognitive difficulties will not be used in this study.
Patients that can not provide the means to be transported home following daily infusions will be excluded from the study.
The investigators feel that issues concerning monetary gain and or loss due to the patient's medical condition may adversely affect the study, therefore, patients with active litigation, compensation or disability issues related to their CRPS will be excluded.
Patients with a history of substance abuse will be excluded.
Patients on certain blood pressure lowering medications such as calcium blockers, or beta blockers will be excluded from the study.
Patients with major medical problems including but not limited to; uncontrolled hypertension, hypotension, cardiac failure, renal failure or liver failure will not be used in this study.

Drexel University College of Medicine Department of Neurology
Philadelphia, Pennsylvania, United States, 19107
Contact: Robert J Schwartzman, MD/Neurology 215-762-7090 rschwartz@drexelmed.edu

6 Pain Exposure Physical Therapy (PEPT) Versus CBO in Patients With Complex Regional Pain Syndrome Type I (CRPS-1)

The current Dutch CBO guideline treatment of Complex Regional Pain Syndrome Type I (CRPS-1) is very disappointing with chronification, disability and subsequent high medical costs and personal suffering. A possible better treatment is intensive function-oriented physical therapy or Pain Exposure in Physical Therapy (PEPT). However, there are no adequate studies performed that demonstrate the efficacy of PEPT and therefore PEPT is lacking in the Dutch CBO CRPS-1 guidelines. Despite a lacking scientific argumentation, the PEPT approach or Macedonian therapy, is now being adopted on a large scale among physical therapists in The Netherlands. There are two level C retrospective cohort studies demonstrating a promising and clinical relevant beneficial effect on pain and function after PEPT. In response to the growing demand for scientific argumentation among doctors and physical therapists with respect to the efficacy of PEPT, we conducted a pilot study at the UMC St Radboud Nijmegen. The results of this pilot study were very promising and therefore, we decided to design a large RCT to investigate the treatment effects and costs in CRPS patients treated with PEPT compared to CRPS patients treated with usual therapy according to the Dutch CBO guidelines.

Inclusion Criteria:

Patients between 18 and 80 years of age with Complex Regional pain Syndrome (CRPS-1) of either upper or lower extremity according to Bruehl's/IASP criteria between 3 and 24 months after initial injury will be selected for the study.

Radboud University Medical Center Recruiting
Nijmegen, Netherlands, 6525 GA
Contact: Jan Paul M Frölke, MD; PhD +31 243613871 j.frolke@chir.umcn.nl

7 Study of Proteins Associated With Complex Regional Pain Syndrome

The etiology of Complex Regional Pain Syndrome (CRPS) is unknown but a patient typically presents with a triad of clinical findings: sensory abnormalities, perfusion abnormalities and alterations in motor function. Since some of these findings are seen in the other disease states, the diagnosis is often not clear. A response to a sympathetic ganglion block (stellate or lumbar) is also suggestive of the disorder. However, there is no definitive diagnostic test for CRPS. Experience has shown that early aggressive treatment improves the prognosis. Therefore, tests that facilitate the early diagnosis would have important clinical implications.

Advances in laboratory techniques allow analysis of clinical samples to identify protein or patterns of protein changes associated with a disease state. Patients suffering with CRPS who are currently seen in a pain clinic will be asked to participate in this study. The subjects will complete a brief symptom survey, be examined by a co-investigator to document sensory, temperature and trophic changes, and have a blood sample collected for protein and gene expression (RNA) analysis. Blood samples from age-matched controls will be collected from non-CRPS patients. Fifty patient samples collected from each group will be analyzed and used to teach the diagnostic software and an additional 20 samples (10 controls, 10 CRPS patients) will be used to validate diagnostic accuracy.

Normal healthy volunteers and patients of any age with complex regional pain syndrome who are in otherwise good general health may be eligible for this study.

Participants will have a medical history, physical examination and collection of a blood sample. They will fill out several questionnaires, providing information on their health, personality, mood, pain levels, and symptoms. Participation in the study requires one outpatient clinic visit.

Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

8 Not yet recruiting The Effect of Transcranial Direct Current Stimulation (t-DCS) On the P300 Component of Event-Related Potentials in Patients With Chronic Neuropathic Pain Due To CRPS or Diabetic Neuropathy

This is a controlled trial designed to determine short- and long-term effects of repeated tDCS on the P300 component of event-related evoked potentials in patients with chronic neuropathic pain due to Complex regional Pain Syndrome (CRPS) or diabetic neuropathy as compared with healthy subjects.

The latency and amplitude of P300, subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined at before and 15 min and 120 min after the 1st and 5th tDCS/sham procedure, To receive tDCS/sham treatment, two electrodes will be placed on the patient´s skull (for details see section Methods) and the patient will rest for 5 min. After that, the patient will receive 20 minutes of 2 mA tDCS/sham. Subjective pain intensity, and pain thresholds for tactile and thermal stimuli will be determined before-, 15 min after and 120 min after each tDCS/Sham procedure. At the 1st and 5th tDCS/Sham session, the latency and amplitude of P300 will be determined before-, 15 min after and 120 min after the tDCS/sham procedure.

Inclusion Criteria:

Patients

Affected an upper limb or lower limb
CRPS-related neuropathic pain with a score for "worst pain in the last 24 hours" ≥4 on a numeric scale 0-10
Must meet CRPS diagnostic criteria (Sandroni et al., 2003) with the application of the IASP criteria as adapted by Bruehl et al (1999):

Continuing pain which is disproportionate to any inciting event,
Must report at least one symptom (symptoms here are reports by subject) in each of the four following categories: sensory, vasomotor, sudomotor/edema, motor/trophic;
Must display at least one sign (signs here refer to objective observation/testing) in in each of the four following categories: sensory, vasomotor, sudomotor/edema, motor/trophic;
tDCS naïve
OR
Affected an upper limb or lower limb
Diabetes-related neuropathic pain with a score for "worst pain in the last 24 hours" ≥4 on a numeric scale 0-10

Control Subjects

Age between 18 and 70 years
No serious health problems
No chronic pain experience for the last six months prior the enrollment
No acute pain of intensity 4 or higher in the last week prior the enrollment
tDCS naïve


Exclusion Criteria:

Patients

Serious health problems other than CRPS or Diabetic Neuropathy (e.g. uncontrolled hypertension, uncontrolled diabetes)
Pain/painful conditions unrelated to CRPS or Diabetic Neuropathy
Pregnancy
History of seizures/epilepsy
Implanted device (e.g. pacemaker)
Active illegal drug/alcohol abuse
Unable to follow directions or complete tools in English
Previous exposure to tDCS stimulation

Control Subjects

Serious health problems (e.g. uncontrolled hypertension, uncontrolled diabetes)
Any painful condition
Pregnancy
History of seizures/epilepsy
Implanted device (e.g. pacemaker)
Active illegal drug/alcohol abuse
Unable to follow directions or complete tools in English
Previous exposure to the tDCS stimulation

9 Not yet recruiting Intravenous Immunoglobulins in Complex-regional Pain Syndrome

CRPS, a chronic pain syndrome associated with trophic disturbances is a frequent complication after limb trauma. More than one third of the CRPS will continue to chronic disease including loss of function in one limb. Some reports implicate an autoimmune pathogenesis of CRPS. Especially the finding of autoantibodies against peripheral neurons and successful treatment in single cases provide evidence for a possible successful treatment of CRPS with intravenous immunoglobulins (IvIg). Therefore IvIg may be an important anti-inflammatory treatment to prevent severe chronification of CRPS. Since IvIg is mainly effective in B-cell-mediated autoimmune diseases, autoantibodies against autonomic neurons and the concentration of B-cell activating factors BAFF and APRIL will be measured in the course of the study.

Inclusion Criteria:

CRPS 1 (according to the IASP criteria) between 6 weeks and 6 months after diagnosis
skin temperature of the affected side equal or higher than on non-affected side
no change of the analgetic or co-analgetic medication within the last 10 days

Exclusion Criteria:

Immunosuppressive or immunomodulatory treatment within the last three months
CRPS previously treated with sympathetic block, lidocaine patch, local DMSO, spinal cord stimulation, intrathecal drug administration
Known immune-mediated neuropathy (CIDP, MMN, MADSAM)
Selective IgA-deficiency
Severe heart disease
Tumour disease in the last 5 years
Allergy against Gamunex 10%
Chronic renal disease Vaccination with live vaccine within the last three months
Member of another clinical trial within the last 3 months

Contact: Franz Blaes, MD +49-641-99(0) ext 45357 franz.blaes@neuro.med.uni-giessen.de
Contact: Marlene Tschernatsch, MD +49-641-99(0) ext 45400 marlene.tschernatsch@neuro.med.uni-giessen.de

Hospital of the Justus-Liebig-University
Giessen, Hessen, Germany, 35392


10 Recruiting Pregabalin Versus Placebo as an Add on for Complex Regional Pain Syndrome (CPRS) of the Upper Limb Managed by Stellate Ganglion Block (The PREGA Study)

Pregabalin group is made up of 20 patients. Patients will receive 150mg/day in two divided does. The patients will be assessed weekly and the dose can be increased to 300mg/day, if the patient does not report any decrease in pain. The following week the dose may be increased to 600mg/day if once again the patient reports no decrease in pain. This is also the maximum permissible does that will be given to the patient. If patient reports any side effects then the dose can be decreased once. The time period of 2 to 5 weeks will be the dose adjustment period. After which the drug maintenance period extends from week 5 to 12. All doses will be given in two divided doses/day.

Inclusion Criteria:

Patients diagnosed with CRPS Type I as per the IASP (International Association for the Study of Pain) criteria which states presence of an initiating noxious event, or cause for immobilization
Evidence at some point of swelling, color change, hot/cold/sweaty sensation and no other condition which can account for the pain and dysfunction of the upper limb
Men or women between ages 18-65 year old
Women should not be pregnant or breast feeding
No change in treatment for 4 weeks prior to recruitment
Pain scores of 4/10 on a verbal analogue scale

Exclusion Criteria:

Patients with a neurologic disorder unrelated to CRPS
Patients who are already on pregabalin
Patients with renal impairment whose creatinine clearance is less than 60 ml/min
Patients with congestive heart failure who are also diabetic and taking thiazolidinedione medication like rivoglitazone
Unstable psychiatric history
Patients with another problem with equal or worse pain
Unstable medical condition

Canada, Ontario
Hamilton General Hospital
Hamilton, Ontario, Canada, L8L 2X2
Contact: Lynda Rickards, RN 905-521-2100 ext 44481 rickard@mcmaster.ca
Principal Investigator: Norman Buckley, MD

11 The Efficacy of Motor Cortex Stimulation for Pain Control

The objective is to determine if motor cortex stimulation works for the following conditions:

Deafferentation facial pain,
Upper extremity complex regional pain syndrome (CRPS) and
Brachial plexus avulsion or phantom limb pain.
Each of these groups of 6 patients (total of 18) will be studied independently and all patients will be implanted with a motor cortex stimulation system. They will be randomised to either a regular or low stimulation setting in the two arms of the study. Each arm will last 3 months.
This is a prospective, blinded randomized crossover study comparing two stimulation paradigms in three different groups of patients receiving motor cortex stimulation. The aim of this study is to examine the effectiveness of this modality in a controlled blinded manner, which has not been done in previous studies. There are two primary purposes of this study. The first is to compare two different stimulation paradigms: "high" level stimulation (i.e. stimulator activated 'on' for 10 minutes, 'off' for 2 hours; presumed therapeutic dose); versus "low" stimulation ('on' for 1 minute, 'off' for 6 hours; presumed subtherapeutic dose), in a prospective blinded crossover study design.

The second purpose of this study, is to examine the outcome of MCS in three different pain groups. These are:

Unilateral upper extremity neuropathic pain such as brachial plexus avulsion, stump pain or phantom limb pain
Neuropathic deafferentation facial pain
Upper extremity complex regional pain syndrome (CRPS)
Measurements of the effects of motor cortex stimulation will include a visual analogue scale (VAS) of perceived pain, the McGill Pain Questionnaire, SF-36 quality of life questionnaire, Beck Depression Inventory-II, the standard 7-point patient global impression of change (PGIC), medications log (verified by pharmacy records) and an employment status questionnaire. Adverse events will be recorded at each visit.

Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Contact: Robert M Brownstone, MD, PhD 902 473 6850 rob.brownstone@dal.ca
Contact: Paula M Chiasson, MSc 902 473 7809 paula.chiasson@cdha.nshealth.ca
Principal Investigator: Robert M Brownstone, MD, PhD

12 Neurotropin to Treat Chronic Neuropathic Pain

*Study start date was September 2000, purportedly to end September 2007.

Patients with Reflex Sympathetic Dystrophy (RSD), re-named Complex Regional Pain Syndrome, type I (CRPS-I), have chronic, post-traumatic pain that spreads beyond the distribution of any single peripheral nerve without evidence of major peripheral nerve damage. A similar disorder, Causalgia, re-named CRPS-II, presents with clear evidence of nerve injury. No successful drug treatment exists for these disorders. Neurotropin is a non-protein extract of cutaneous tissue from rabbits inoculated with vaccinia virus. Neurotropin has been used extensively in Japan to treat RSD and other painful conditions; however, the drug has not undergone clinical therapeutic testing in the United States. This protocol is to carry out double-blind, placebo-controlled, crossover studies about clinical efficacy of Neurotropin for acute pain in dental outpatients and for chronic pain in outpatients with CRPS-I or II.

Patients with CRPS I and II will receive an individualized regimen of physical therapy and standard treatment to control their pain. In addition, they will receive neurotropin or placebo tablets for 5 weeks, then no trial medicine for at least 1 week, and then the other trial drug for the next 5 weeks. That is, patients who took placebo the first 5 weeks will take neurotropin the second 5 weeks and vice versa. Neither the patients nor the doctors will know who received which drug during the two intervals until the study is over. Patients will complete questionnaires about their pain, quality of life, and ability to perform daily living activities. They will have various tests to measure pain (such as sensitivity to heat and cold, to an electric current, to a mild pin prick, etc.); to provide information about changes in their condition (such as tests of range of motion of joints and limb size); to measure blood circulation and sweating in the arm or leg (such as measurements of blood flow to the limb, skin temperature, and sweat production), and other procedures.

INCLUSION CRITERIA:
Dental outpatients undergoing elective removal of impacted third molars based on a preoperative diagnosis of the type and number of teeth to be extracted. The difficulty of extraction will be classified based on clinical exam and a panoramic radiograph as simple extraction (1), soft tissue impaction (2), partial boney impaction (3), or full boney impaction (4). Both lower teeth to be extracted should be similarly boney impacted, and the score for each of the two lower teeth should be 3 to 4. Uppers are usually in soft tissue. The diagnosis for each tooth will be confirmed by the oral surgeon after the procedure based on the surgical procedure actually performed.

CRPS patients are referred with a diagnosis of CRPS-I or CRPS-II in one limb only, based on pain (1) that is post-traumatic and spread beyond the region of the injury; (2) has persisted for more than 2 weeks; and (3) is associated with swelling, altered skin color or skin temperature, altered sweating, allodynia or hyperesthesia or limitation of active movement. Atrophic changes in skin, hair loss or nail changes, or disuse atrophy of skeletal muscle may be present.

Both sexes are to be studied.

All ethnic and racial groups can participate.

Patients must be willing to return to NIH for follow-up evaluation under this protocol.

EXCLUSION CRITERIA:

Dental outpatients must not be taking any medications chronically (with the exception of oral contraceptive agents).

Pregnant and lactating women are excluded.

Based on the oral surgeon's postoperative diagnosis, any extraction which is classified as producing unusual surgical trauma will result in exclusion from the remainder of the study.

Dental subjects will also be excluded if they are not adequately sedated by midazolam alone and require intraoperative administration of an opioid drug such as fentanyl, administration of greater than 14.4 ml of local anesthetic (2% lidocaine with 1:100,000 epinephrine), or postoperative administration of a steroid for possible injury to the inferior alveolar nerve.

Patients referred with CRPS-I or CRPS II who have abnormal screening test results or who have non-traumatic disorders to which pain may be attributed (gout, malignancy, arthritis, etc.) will be excluded.

Any patients who have had ablative procedures for treatment of their neuropathic pain disorder will not be eligible for inclusion in this study.

Patients who have a positive HIV result will be excluded.

Subjects with obviously impaired mental capacity that precludes informed consent and ability to provide adequate self-ratings are to be excluded.

CONTACT INFO:
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov


Background info on Neurotropin:
The Antiallodynic and Antihyperalgesic Effects of Neurotropin® in Mice with Spinal Nerve Ligation

13 Evaluation and Diagnosis of People With Pain and Fatigue Syndromes

NO TREATMENT OFFERED THROUGH THIS CLINICAL TRIAL

This screening protocol is designed to facilitate patient recruitment to the National Institute of Nursing Research (NINR) clinical research studies on pain and fatigue syndromes. Patients must meet the specific requirements of an IRB-approved research study; this protocol serves as a first step for evaluating patients for possible inclusion in a natural history or intervention protocol.

Candidates will be screened with medical history/physical examination, routine laboratory tests, and questionnaires. The physical examination may include the standardized tender point assessment as specified in the American College of Rheumatology (ACR) to diagnose fibromyalgia, measurements of pain (allodynia, hyperalgesia, and hyperpathia), edema, autonomic dysfunction (altered skin color, temperature, or sudomotor activity), and extent of musculoskeletal dysfunction by doing strength tests (i.e. hand grips), walk tests (6-minute walk test), physical activity monitoring (portable activity monitor), and exercise test. It will also assess the patients' level of pain, fatigue, and quality of life by providing questionnaires for the patients to complete. When the screening is completed, patients will be informed of their options to participate in other NINR interventional or observational clinical research studies. Patients who are not eligible for these studies will be informed of alternative treatments. No treatment is offered under this protocol. Information collected in this protocol will be used to determine eligibility to other NINR protocols.

INCLUSION CRITERIA:
Are greater than or equal to 18 years of age;
Have symptoms of pain and/or fatigue.

EXCLUSION CRITERIA:
Inability to provide informed consent for the study;
Are unwilling or unable to cooperate with the study procedures or travel to NIH for the procedures.

CONTACT:
Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

14 Regional Anesthesia Military Battlefield Pain Outcomes Study

Sponsor -- Dept of Veteran Affairs
Collaborators -- Walter Reed Army Medical Center, Brooke Army Medical Center

BACKGROUND:

Adequate pain management for combat casualties balances the need for emergent, life-saving care with the urgency to remove soldiers from harm's way. Control of pain in traumatic battlefield situations may be impossible until safe evacuation to a surgical facility is achieved and a wounded soldier can receive general anesthesia. Recent evidence suggests that neural plasticity in the central nervous system coupled with hyperstimulation of central neuronal pathways lead to neuropathological remodeling. This neural rewiring may result in chronic pain for patients who have experienced severe, unrelieved acute pain. In addition, the stress of combat along with the suffering of prolonged uncontrolled pain may contribute to psychological disorders, such as post-traumatic stress disorder, depression, and substance abuse.

OBJECTIVE:

The purpose of this study is to evaluate the effect of early and aggressive advanced regional anesthesia on the chronic neuropathic pain, health related quality of life, and mental health of OEF/OIF veterans who have suffered a major limb injury in combat. An additional aim of this study is to quantify and characterize the short-term and long-term effects of traumatic combat limb injuries on post-injury acute pain, chronic pain, health related quality of life, functional status, social reintegration, psychological adjustment, and substance abuse behaviors in a population of injured military personnel.

METHOD:

This study employs a cohort repeated measures study design involving prospective data collection at scheduled intervals. Interviews with participants provide data on pain outcomes, psychiatric morbidities, and quality of life. Follow up evaluations conclude at the two year anniversary of the start of combat injury rehabilitation. Medical records information collected retrospectively from armed services treatment facilities provide data on the use of pain management therapies as well as individual responses to regional anesthesia.

IMPLICATIONS FOR RESULTS:

The findings of this study may impact the clinical field by providing information on the effectiveness and benefits of early advanced regional anesthesia for chronic pain control. This study may also provide data to determine whether regional anesthesia pain treatments prevent or reduce the development of psychological maladjustment disorders such as post-traumatic stress disorder, depression, and substance abuse in a population of military personnel with combat limb injuries.

Study Population:
Soldiers with one or more mangled or amputated limbs from Iraq/Afghanistan war.

Inclusion Criteria:

Major injury in one or more extremities requiring hospitalization and inpatient rehabilitation.

Exclusion Criteria:

Major head trauma,
Cognitive deficits,
Inability to concentrate
Poor judgment and impulse control,
Substantial hearing loss
Bilateral upper extremity amputation with no alternate means to complete the survey forms

Contact: Yolanda S Williams, MPH (215) 823-5800 ext 2774 yolanda.williams5@va.gov
Contact: Holly Luu, BA (215) 823-5800 ext 6506 holly.luu@va.gov

Locations:

United States, District of Columbia
Walter Reed Army Medical Center Recruiting
Washington, District of Columbia, United States, 20307
Contact: Lt. Col. Chester C Buckenmaier III, MD 202-782-7652

United States, Pennsylvania
Pain Management Service Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lynn A Watson (215) 823-5800 ext 6023 lynn.watson@va.gov
Contact: Yvette Roberts (215) 823-5800 ext 6020 yvette.roberts@va.gov
Principal Investigator: Rollin McCulloch Gallagher, MD MPH

United States, Texas
Brooke Army Medical Center Not yet recruiting
Fort Sam Houston, Texas, United States, 78234
Contact: Cpt. Laura McGhee, PhD 210-916-5482

EDITORIAL RANT: SEARCH ENGINES STILL RETRIEVE THE FRAUDULENT WORK OF DICKHEAD DOCTOR SCOTT REUBEN AS THE BEST RESPONSE TO A SEARCH USING THE TERMS "REGIONAL ANESTHESIA AND CRPS." grrrrr...

Additional reading:

American Pain Foundation -- Battlefield Medicine and Combat Trauma: New Approaches to Pain Relief, September 9, 2005, Lt. Col. Chester C. Buckenmaier III, MD

Anesthesia and Perioperative Care/Textbook of Military Medicine

15 Susceptibility to Chronic Post-Traumatic Extremity Pain

This will be a prospective association study in which we will recruit patients who have experienced single extremity trauma, or who have scheduled elective surgery on a single extremity. HRQoL will be determined at recruitment. We will identify their haplotypes and genotypes for 4 linked SNPs in the coding region of COMT as described by Diatchenko [2]. Patients will receive follow-up at 3 and 6 months following trauma or surgery. Individuals who report either neuropathic pain or a reduced HRQoL score will be more closely examined, in order to identify CPSP or CRPS. Statistical analyses will be performed to determine whether haplotypes are associated with the development of either condition, and to determine the strength of this association.

Study Population:
Patients undergoing shoulder surgery

Inclusion Criteria:
Provide written Informed Consent prior to participation in the study
Be at lease 18, but not more than 80 years of age
Have the ability to read and understand the study procedures and the use of the pain scales and have the ability to communicate meaningfully with the Study Investigator and staff.
Be free of other physical, mental, or medical conditions, which, in the opinion of the Investigator, makes Study participation inadvisable
Is scheduled to undergo open or arthroscopic shoulder surgery
If the subject is a female of childbearing potential, have a negative pregnancy test on the day of surgery.

Exclusion Criteria:
- Has significant medical disease(s), laboratory abnormalities or conditions(s) that in the Investigator's judgment could compromise the Subject's welfare, ability to communicate with the Study staff, complete Study activities, or would otherwise contraindicate Study participation

Locations
United States, Michigan
William Beaumont Hospitals
Royal Oak, Michigan, United States, 48073
Contact: Cecile Pestano, RN 248-898-1907 cpestano@beaumont.edu
Contact: Nickole Carlson, RN 248-898-1907 ncarlson@beaumont.edu

William Beaumont Hospital
Troy, Michigan, United States, 48085
Contact: Cecile Pestano, RN 248-964-3440 cpestano@beaumont.edu
Contact: Nickole Carlson, RN 248-898-1907 ncarlson@beaumont.edu

Additional reading: The Internet Journal of Anesthesiology 2008 : Volume 15 Number 2
Chronic Post-surgical Pain: Prevention remains better than cure
Alfred Philip James Lake FFARCS

16 Effect of an Educational Intervention on Cardiac Patients' Participation Rate in Cardiac Rehabilitation Programs DESPITE MY BEST EFFORTS, THEY KEEP RELISTING THIS STUDY. CRP = CARDIAC REHAB PROGRAMS, NOT CRPS

17 Not yet recruiting Efficacy of Etoricoxib on Peripheral Hyperalgesia

Animal experiments analysing anti-hyperalgesic effects of Coxibs show inconsistent results due to different used dosages and varying different pain models. Theoretical the use of NSAIDs is rational, particularly of Coxibs as a part of the neuropathic pain management. But in the newest topical review, there is no valid information available about the effectiveness of these drugs in human neuropathic pain models or in patients with different underlying mechanism, e.g. with or without hyperalgesia.

Inclusion Criteria:

Patients over 18 years with
Persistent moderate or severe pain (> 4 on NRS (1..10)) at rest (average of three daily assessments using a diary for at least two days) .
Neuropathic pain associated with a clinical and neurologically proven peripheral nerve injury, radiculopathy, postherpetic neuralgia or polyneuropathy or CRPS
One of the two following QST phenotypes at the baseline assessment:

signs of peripheral hyperalgesia (that means, pathological decreased heat pain threshold and/or pathological decreased muscle pain threshold)
without signs of peripheral hyperalgesia (no pathological decreased heat - and/or muscle pain threshold)
Patients of both gender
Signed consent form
Patients with the ability to understand and follow the instructions of the doctor

Exclusion Criteria:

Excluded will be patients Parkinson's disease or a history of cerebral vascular insult or nerve injury.

Excluded will be also all patients with contradictions for the use of Etoricoxib:

Hypersensitivity to the active substance or to any of the excipients.
Active peptic ulceration or active gastrointestinal (GI) bleeding.
Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetyl-salicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
Pregnancy and lactation
Severe hepatic dysfunction

Additional Reading: Interaction of Hyperalgesia and Sensory Loss in Complex Regional Pain Syndrome Type I (CRPS I)

Pharmacologic Therapies for Complex Regional Pain Syndrome, Sean Mackey, MD, PhD, and Steven Feinberg, MD, MPH

18 Cerebrospinal Fluid Repository

The only specific procedures unique to this protocol is the collection of an additional 3ml or less of cerebrospinal fluid from a lumbar puncture already being performed and the collection of clinical information from the patients medical records. Lumbar puncture may be either a research procedure or a standard of care procedure, depending upon the reason for initiating the puncture. We will aliquot the additional fluid into a separate storage container and it will be maintained in the laboratory of Dr. Heiman-Patterson at -70 degrees. Clinical information including age, medical and neurological history, laboratory data, and pathologic information where indicated will be abstracted from the patient chart. All specimens and corresponding clinical information will be labeled with an identification number and sorted by diagnosis. There will be no patient identifying information kept with the specimens. The CSF sample may be used for studies performed by researchers at Drexel University College of Medicine or shared with collaborators. The CSF sample provided will only be used for projects that have approval by the IRB, but subjects will not be notified each time it is used for a study. If CSF sample is still available, consent can be withdrawn at any time by writing a letter to Dr. Heiman-Patterson requesting the withdrawal of the sample.

Researchers will request control and disease specific samples to use in various research studies. There are no DNA studies.

Inclusion Criteria:

Any person undergoing a diagnostic lumbar puncture with a neurologic illness
Any person undergoing a lumbar puncture as part of anesthesia
Any person who is undergoing a lumbar puncture for other research purposes such as clinical trials and who has already consented to the lumbar puncture for that purpose.

MDA/ALS Center of Hope
Philadelphia, Pennsylvania, United States, 19104
Contact: Christine Barr, RN 215-762-5186 cbarr@drexelmed.edu
Principal Investigator: Terry Heiman-Patterson, MD

19 Transcranial Magnetic Stimulation (TMS) Effects on Pain Perception

Chronic pain represents a huge public health concern and is generally poorly understood at a basic neurobiological level. Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses electromagnetic pulses to temporarily stimulate specific brain areas in awake people (without the need for surgery, anesthesia, or other invasive procedures). Previous research suggests that TMS may be effective in reducing pain perception in healthy adults and in patients with various types of pain conditions, such as neuropathic pain. However, there is relatively little research on TMS and pain that addresses optimal TMS device parameters, optimal cortical targets, and potential differences in response to TMS between healthy persons and those with chronic pain.

The purpose of this trial is to study the effects of TMS on pain perception. Specifically, this study will determine optimal device parameters (dose) and brain targets for stimulation with TMS in order to reduce pain in patients with neuropathic pain and in healthy adults using laboratory pain methods.

Participants with Neuropathic Pain:

After an initial screening, eligible participants with neuropathic pain will receive a magnetic resonance imaging (MRI) scan to help determine the best target for TMS stimulation later in the study. Participants will be asked to record their pain experiences every day for 2 weeks before receiving the first of 2 laboratory pain assessments. The laboratory pain assessment uses a small device, controlled by a computer and attached to the underside of the forearm, to produce different temperature stimulations. As the device reaches a level considered painful to the participant, he/she can push a button to return to a level of comfort.

The next part of the trial involves two, 20-minute TMS treatment sessions per day for 5-days. Participants will be randomly assigned to one of two groups. Group A will receive real TMS and Group B will receive "sham" TMS. Study participation time for individuals with TGN is about 8 weeks, including about 10 hours (7 visits) at the Medical University of South Carolina (MUSC).

Healthy Volunteers:

In addition to an interview with researchers regarding medical history, healthy participants will complete a self-report screening to assess pain history and level of depression and anxiety. Eligible participants will be given a laboratory pain assessment, and be randomly assigned to one of two groups: group A will receive real TMS and group B will receive "sham" TMS. After TMS, participants will receive another full laboratory pain assessment and complete questionnaires. For healthy volunteers, participation in the study will take about 3 hours and may be completed in one or two visits.

Inclusion Criteria:

For Healthy Adults:
Between age of 21 and 75
No prescription medications in previous 3 months
No seizure history
No depression
Not suicidal
No anxiety
No hospitalizations or surgeries in previous 6 months
No history of chronic pain conditions
No implanted metal devices (e.g., pacemakers, metal plates, wires)
Not pregnant
No alcohol abuse/dependence history in previous 6 months
No illicit drug use in previous 6 months
Capable of reading, writing, giving consent, following instructions
No history of brain surgery or history of loss of consciousness >15 minutes
No history of autoimmune or endocrine disorder
No significant anxiety about entering MRI scanner

For Patients with neuropathic pain:
Between age of 21 and 75
No seizure history
Not taking medications shown to increase seizure risk (6 months)
Not suicidal
No hospitalizations or surgeries in previous 3 months
No implanted metal devices (e.g., pacemakers, metal plates, wires)
Not pregnant
No alcohol abuse/dependence history in previous 6 months
No illicit drug use in previous 6 months
Capable of reading, writing, giving consent, following instructions
Chronic pain (>6 months), not significantly relieved by pharmacological treatment
No significant anxiety about entering MRI scanner

Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences Medical University of South Carolina 5-North, IOP, 67 President Street
Charleston, South Carolina, United States, 29425
Contact: Jeffrey J Borckardt, Ph.D. 843-876-5142 borckard@musc.edu
Principal Investigator: Jeffrey J. Borckardt, Ph.D.

Additional reading:
Sensorimotor integration in Complex Regional Pain Syndrome: A transcranial magnetic stimulation study
Pain, Volume 127, Issue 3, Pages 270-275
A. Turton, C. McCabe, N. Harris, S. Filipovic

General article on Wikipedia

20 Effects of Vaporized Marijuana on Neuropathic Pain

The case for marijuana's medical use for pain is primarily from experimental studies with normal subjects, which have yielded conflicting results. Experimental subjects have been shown to have significant dose-dependant antinociception effect that is not reversed by opioid antagonism. In contrast to this positive antinociceptive effect, other experiments demonstrated hyperalgesic activity and probably enhancement of the perception of pain upon acute exposure in chronic users of marijuana.

In addition to studying spontaneous pain antinociception, it would be useful to evaluate the response to marijuana following evoked pain. Such evoked pain is produced by stimulation of the skin that is normally not noxious.

Because of the potential side effects of marijuana administration, one of the aims of the present study is to analyze inter-individual variability and the occurrence of dose-dependant analgesia of marijuana with an eye on defining tolerable dosing in clinical neuropathic pain syndromes.

Comparisons: Neuropathic and experimentally induced pain scores will be compared after the administration of escalating doses of low, high, and placebo marijuana cigarettes as provided by the National Institutes on Drug Abuse (NIDA).

Inclusion Criteria:

Age greater than 18 and less than 70
Visual Analogue Scale (VAS pain intensity) greater than 3/10
A negative urine drug screening test, i.e., no evidence of IV drug abuse
Neuropathic pain due to reflex sympathetic dystrophy, peripheral neuropathy, post-herpetic neuralgia, post-stroke pain, multiple sclerosis or spinal cord injury

Exclusion Criteria:

Presence of another painful condition of greater severity than the neuropathic pain condition which is being studied.
Subjects with moderate-severe major depression, bipolar/mania, bipolar II/hypomania and schizophrenia or schizoaffective disorder.
Unstable Type 1 or 2 diabetes defined as blood glucose more than 156 mg/dl
History of traumatic brain injury
Uncontrolled medical condition, including coronary artery disease, hypertension, cerebrovascular disease, asthma, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), opportunistic infection, malignancy requiring active treatment, active substance abuse (alcohol or injection drugs).
Current use of marijuana (e.g., within 30 days of randomization)
Pregnancy as ascertained by a self-report and a mandatory commercial pregnancy test.

Contact: Staci M. Sakai, BS 916-734-2935 smsakai@ucdavis.edu

United States, California
CTSC Clinical Research Center, Sacramento VA Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Laurie Vazquez, RN, MSN, FNP 916-843-9436 laurie.vazquez@ucdmc.ucdavis.edu