St. John's Wort in the Treatment of Raynaud's Phenomenon

Study Overview
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Brief Summary
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This trial will test the efficacy of St. John's Wort (SJW) as a supplement, in the treatment of Raynaud's phenomenon (RP). The investigators are hypothesizing that taking SJW 300mg, 3 times a day will decrease the frequency, duration, and severity of RP attacks when compared to placebo. Patients with RP will answer questionnaires and self-evaluate their symptoms of RP as a baseline. Then they will be assigned to either a treatment (will receive SJW capsules) or placebo (will receive non-therapeutic capsules) group. They will be required to take their capsules, self-evaluate their progress and be evaluated every two weeks in a clinic. The treatment phase will last six weeks. This trial will be conducted in a way to mimic the normal usage of natural products. Patients will not be required to stop any current treatment for RP.

Detailed Description
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Raynaud's Phenomenon (RP) is a common vasospastic problem of digital artery vessels causing pain and ischemic fingers (the fingers turn white and then blue and or red). It is considered primary when it is not associated with other conditions. Raynaud's symptoms that are associated with pathological underlying cause especially connective tissue diseases are defined as secondary Raynaud's and are usually more severe than primary symptoms. Selective Serotonin receptor inhibitors (SSRIs) have shown to be effective in decreasing the symptoms of RP. St. John's Wort (SJW) is an natural product that is presently approved by Health Canada for treatment of depression. It is believed that SJW would have mechanism of action very similar to SSRIs. This clinical trial will measure the efficiency of SJW in decreasing the frequency, duration and severity of RP attacks. SJW will be test as a supplement to other treatments already in place. 76 patients (38 with primary Raynaud's and half with secondary Raynaud's) will be recruited from the Rheumatology clinic of St. Joseph's Health Care in London, Ontario. The recruitment period will span 18 months. As they enter the trial, subjects will be assigned to a treatment or a placebo group according to a pre-set randomization schedule. This assignment will be stratified for primary or secondary Raynaud's and double-blinded (patient and investigator). The primary outcome measure (frequency, duration and severity) will be assessed by the patient on a daily basis using a journal provided by the investigator. Secondary outcome measures will include functions questionnaires (HAQ, SF-36, DASH) and biological markers of endothelial damage (V-CAM, I-CAM, VEGF, von Willebrand factor), will be conducted as a baseline and at the conclusion of the treatment phase. Patients participation will span 8-10 weeks. The first two weeks are a baseline measurement for the status of RP using the journals, questionnaires, and serum tests. The treatment period will last 6 weeks in which the subject will be taking the capsules that they have been assigned and will be evaluated for changes or side-effects every two weeks. At the last visit the questionnaires and serum test will be repeated. Other results which may arise from the trial are: The safety of SJW in rheumatology patients, by monitoring side-effects The attitude of rheumatology patients in using Natural Health Products, by a questionnaire Elucidating parts of the RP mechanism, by measuring bio-markers Differences between primary and secondary RP, by stratified randomization The results will be analyzed for all three primary outcome measures as a difference of between baseline and treatment. These differences will be compared between treatment and placebo and each will be stratified for primary vs. secondary and possibly other demographic data. This trial, if positive, will offer another treatment to RP patients. This option will possibly have less side-effects and be better accepted because it is a Natural Product.

Official Title
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A Randomized, Placebo-controlled Trial of St.John's Wort(a Natural Health Product) in the Treatment on Raynaud's Phenomenon

Conditions
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Raynaud's Disease

Intervention / Treatment
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* Drug: St. John's Wort
* Drug: Lactose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or Females between 16 and 70 years old Primary or secondary Raynaud's phenomenon, as diagnosed by a rheumatologist Clinical need for treatment of Raynaud's phenomenon Experiences at least 7 attacks per week Willing and able to provide informed consent Exclusion Criteria: Prior allergic reaction to St. John's Wort Pregnancy or possibility or pregnancy in the next 4 months Women that are currently breastfeeding Depression requiring treatment Use of SSRIs or other antidepressants with the exception of low dose amitriptyline used for reasons other than depression Use of drugs that are potentiated by St. John's Wort, such as cyclosporine, coumadin, digoxin, and theophylline. The complete list of contraindicated medications can be received from investigator Clinically significant non-compliance with past therapies Anticipated need for surgery (sympathectomy) in the next three months

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>St. John's wort 300mg PO TID | Drug: St. John's Wort<br>* SJW in capsule form 300 mg PO TID<br>* Other names: Webber natural brand, product number 5006.;|
| Placebo Comparator: 2<br>Lactose in capsule matching the St. John's wort. 300mg PO TID | Drug: Lactose<br>* lactose in gelatin capsule that same as St. John's wort<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Raynaud's Phenomenon (RP) attacks |  | 6 weeks | 
| Duration of RP attacks |  | 6 weeks | 
| Severity of RP attacks |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily functions questionnaires (HAQ, SF-36, DASH) |  | 6 weeks | 
| Biological markers of endothelial damage (V-CAM, I-CAM, VEGF, etc.) |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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St. John's Wort, Selective Serotonin Receptor Inhibitor, Microvasculature, Natural Health Products