Raynaud's DiseasePhase 3NCT00351117
St. John's Wort in the Treatment of Raynaud's Phenomenon
A Phase 3 study testing St. John's Wort and Lactose in people with Raynaud's Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Raynaud's Disease
- What is being tested?
- St. John's Wort and Lactose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2007to Aug 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Rheumatology Clinic, St. Joseph's Health Care
London, Ontario, N6A 4V2
About this study
Official title: A Randomized, Placebo-controlled Trial of St.John's Wort(a Natural Health Product) in the Treatment on Raynaud's Phenomenon
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.
Read the 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.
- Conditions
- Raynaud's Disease
- Being tested
- St. John's Wort, Lactose
- Keywords
- St. John's Wort, Selective Serotonin Receptor Inhibitor, Microvasculature, Natural Health Products
- Medical subject headings
- Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
St. John's WortDrug
Also called Webber natural brand, product number 5006.
SJW in capsule form 300 mg PO TID
LactoseDrug
lactose in gelatin capsule that same as St. John's wort
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | St. John's wort 300mg PO TID Receives: Drug: St. John's Wort |
| 2 | Placebo comparator | Lactose in capsule matching the St. John's wort. 300mg PO TID Receives: Drug: Lactose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Raynaud's Phenomenon (RP) attacks
Measured: 6 weeks
Duration of RP attacks
Measured: 6 weeks
Severity of RP attacks
Measured: 6 weeks
Secondary outcomes (2)
Daily functions questionnaires (HAQ, SF-36, DASH)
Measured: 6 weeks
Biological markers of endothelial damage (V-CAM, I-CAM, VEGF, etc.)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2006 (estimated)
- Study startMar 2007
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Raynaud's DiseaseStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Investigators
- Janet E Pope, MD, MPH, Principal investigator, Associate Professor of Medicine University of Western Ontario
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00351117
- Sponsor's protocol ID
- R-06-355
- Other IDs
- 250347647
- Status last verified
- Jul 2009
- First submitted
- 11 Jul 2006
- Last updated
- 14 Jul 2009
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1097/00004850-200015020-00001.
PubMed 10759336Coleiro 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. doi: 10.1093/rheumatology/40.9.1038.
PubMed 11561116Pope J. Raynaud's phenomenon (primary). Clin Evid. 2003 Jun;(9):1339-48. No abstract available.
PubMed 12967424Bolte MA, Avery D. Case of fluoxetine-induced remission of Raynaud's phenomenon--a case report. Angiology. 1993 Feb;44(2):161-3. doi: 10.1177/000331979304400213. No abstract available.
PubMed 8434812Brenner 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. doi: 10.1016/S0149-2918(00)89010-4.
PubMed 10823363Pope 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.
PubMed 14705233Jaffe IA. Serotonin reuptake inhibitors in Raynaud's phenomenon. Lancet. 1995 May 27;345(8961):1378. doi: 10.1016/s0140-6736(95)92582-1. No abstract available.
PubMed 7752794Knuppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004 Nov;65(11):1470-9. doi: 10.4088/jcp.v65n1105.
PubMed 15554758Lecrubier 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. doi: 10.1176/appi.ajp.159.8.1361.
PubMed 12153829
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled Trial of St.John's Wort(a Natural Health Product) in the Treatment on Raynaud's Phenomenon
- ClinicalTrials.gov ID
- NCT00351117
- Acronym / sponsor ID
- R-06-355
- Conditions
- Raynaud's Disease
- Keywords
- St. John's Wort, Selective Serotonin Receptor Inhibitor, Microvasculature, Natural Health Products
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 12 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: St. John's WortSt. John's wort 300mg PO TID |
| 2 | Placebo comparator | Drug: LactoseLactose in capsule matching the St. John's wort. 300mg PO TID |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| St. John's WortAlso: Webber natural brand, product number 5006.SJW in capsule form 300 mg PO TID | Drug | 1 |
| Lactoselactose in gelatin capsule that same as St. John's wort | Drug | 2 |
Primary outcome
Frequency of Raynaud's Phenomenon (RP) attacks
Time frame: 6 weeks
Duration of RP attacks
Time frame: 6 weeks
Severity of RP attacks
Time frame: 6 weeks
2 secondary outcomes
Daily functions questionnaires (HAQ, SF-36, DASH)
Time frame: 6 weeks
Biological markers of endothelial damage (V-CAM, I-CAM, VEGF, etc.)
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2009.
- Background: PubMed 10759336Schrader 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. doi: 10.1097/00004850-200015020-00001.
- Background: PubMed 11561116Coleiro 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. doi: 10.1093/rheumatology/40.9.1038.
- Background: PubMed 12967424Pope J. Raynaud's phenomenon (primary). Clin Evid. 2003 Jun;(9):1339-48. No abstract available.
- Background: PubMed 8434812Bolte MA, Avery D. Case of fluoxetine-induced remission of Raynaud's phenomenon--a case report. Angiology. 1993 Feb;44(2):161-3. doi: 10.1177/000331979304400213. No abstract available.
- Background: PubMed 10823363Brenner 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. doi: 10.1016/S0149-2918(00)89010-4.
- Background: PubMed 14705233Pope 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.
- Background: PubMed 7752794Jaffe IA. Serotonin reuptake inhibitors in Raynaud's phenomenon. Lancet. 1995 May 27;345(8961):1378. doi: 10.1016/s0140-6736(95)92582-1. No abstract available.
- Background: PubMed 15554758Knuppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004 Nov;65(11):1470-9. doi: 10.4088/jcp.v65n1105.
- Background: PubMed 12153829Lecrubier 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. doi: 10.1176/appi.ajp.159.8.1361.
- American website of institute of arthritis: general medical information on Raynaud's DiseaseLink provided by the sponsor.
- Canadian complementary and alternative medicine research group: contains details on how to conduct a natural product trials and has a lot of resources.Link provided by the sponsor.
- A database that is linked to MedLine and does searches for herbal medicine only.Link provided by the sponsor.
- Health Canada Natural Health product site: information on regulation and legislatureLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet E Pope, MD, MPH principal investigator
Associate Professor of Medicine University of Western Ontario
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing St. John's Wort and Lactose in people with Raynaud's Disease, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Raynaud's Phenomenon (RP) attacks (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00351117, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2009.