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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Raynaud's Disease	Drug: St. John's Wort; Drug: Lactose	Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Placebo-controlled Trial of St.John's Wort(a Natural Health Product) in the Treatment on Raynaud's Phenomenon
Study Start Date :	March 2007
Actual Primary Completion Date :	August 2008
Actual Study Completion Date :	August 2008

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 1; St. John's wort 300mg PO TID	Drug: St. John's Wort; SJW in capsule form 300 mg PO TID; Other Name: Webber natural brand, product number 5006.
Placebo Comparator: 2; Lactose in capsule matching the St. John's wort. 300mg PO TID	Drug: Lactose; lactose in gelatin capsule that same as St. John's wort

Outcome Measures

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Primary Outcome Measures :

1. Frequency of Raynaud's Phenomenon (RP) attacks [ Time Frame: 6 weeks ]
2. Duration of RP attacks [ Time Frame: 6 weeks ]
3. Severity of RP attacks [ Time Frame: 6 weeks ]

Secondary Outcome Measures :

1. Daily functions questionnaires (HAQ, SF-36, DASH) [ Time Frame: 6 weeks ]
2. Biological markers of endothelial damage (V-CAM, I-CAM, VEGF, etc.) [ Time Frame: 6 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 70 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Canada, Ontario
Rheumatology Clinic, St. Joseph's Health Care
London, Ontario, Canada, N6A 4V2

Sponsors and Collaborators

Lawson Health Research Institute

Investigators

Principal Investigator:	Janet E Pope, MD, MPH	Associate Professor of Medicine University of Western Ontario

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

American website of institute of arthritis: general medical information on Raynaud's Disease 

British site for Raynaud's patients: cover medical data as well as support programs 

Canadian complementary and alternative medicine research group: contains details on how to conduct a natural product trials and has a lot of resources. 

A database that is linked to MedLine and does searches for herbal medicine only. 

Health Canada Natural Health product site: information on regulation and legislature 

Publications:

Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. 2000 Mar;15(2):61-8.

Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, Black CM. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford). 2001 Sep;40(9):1038-43.

Pope J. Raynaud's phenomenon (primary). Clin Evid. 2003 Jun;(9):1339-48. Review. Update in: Clin Evid. 2003 Dec;(10):1444-53.

Bolte MA, Avery D. Case of fluoxetine-induced remission of Raynaud's phenomenon--a case report. Angiology. 1993 Feb;44(2):161-3.

Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. 2000 Apr;22(4):411-9.

Pope JE, Prashker M, Anderson J. The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis. J Rheumatol. 2004 Jan;31(1):140-9.

Jaffe IA. Serotonin reuptake inhibitors in Raynaud's phenomenon. Lancet. 1995 May 27;345(8961):1378.

Knüppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004 Nov;65(11):1470-9. Review.

Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002 Aug;159(8):1361-6.

Responsible Party:	Janet Pope, Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT00351117 History of Changes
Other Study ID Numbers:	R-06-355; 250347647
First Posted:	July 12, 2006
Last Update Posted:	July 14, 2009
Last Verified:	July 2009

Keywords provided by Lawson Health Research Institute:

St. John's Wort; Selective Serotonin Receptor Inhibitor; Microvasculature; Natural Health Products

Additional relevant MeSH terms:

Raynaud Disease; Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases