Clinical trial NCT02506062: A Trial of Ischemic Preconditioning in Raynaud's Phenomenon (RP)
Official title: A Randomized, Single-blinded Placebo-controlled Trial of Ischemic Preconditioning in Raynaud's Phenomenon (RP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Raynaud Disease
Raynaud's Phenomenon
Keywords: ischemic preconditioning
Raynaud's Phenomenon
(RP)
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2015-07-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This trial will test the efficacy of brief periods of controlled limb ischemia (remote ischemic preconditioning, RIPC) as an effective treatment of patients with Raynaud's Phenomenon (RP).The hypothesis of this trial is that due to its vasoprotective effects, RIPC would be more effective than placebo in the treatment of both primary and secondary RP, as defined by decreased frequency, duration, and severity of attacks. This trial was also designed to monitor the tolerance of RIPC in a rheumatologic population. Patients will not be required to stop any current treatment for RP.

Detailed description: Raynaud's phenomenon (RP) is defined as vasospasms of arteries causing pallor and at least one other color change upon reperfusion such as cyanosis or redness. The current treatments for RP (channel blockers, PDE5 inhibitors, etc.) have only modest efficacy and are associated with many side-effects including headaches, flushing, hypotension and fluid retention that require stopping the medication. Thus, identification of an innovative treatment is an important therapeutic goal in RP patients.

Ischemic preconditioning is a simple non-invasive procedure which consists of 4 consecutive episodes of brief ischemia caused by placing a pneumatic cuff at the level of the brachial artery and inflating it to 200 mm Hg for 2.5 minutes, followed by 2.5 minutes of reperfusion. Over 20 years IPC has generated tremendous scientific interest being described as the most powerful available form of in vivo protection against ischemic injury.

This clinical trial will measure the efficiency of RIPC in decreasing the frequency, duration and severity of RP attacks. 24 patients will be recruited from the Rheumatology clinic of St. Joseph's Health Care in London, Ontario. As they enter the trial, subjects will be assigned to a treatment or a placebo group according to a pre-set randomization schedule. The trial will be single-blinded (patient).

The primary outcome measures (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 (Raynaud's Condition Score, s-HAQ-DI, DASH) and biological markers of endothelial damage (P-selectin, I-CAM, VEGF), will be conducted every two weeks: at baseline, post-placebo, post-washout, and post-treatment phases.

Patients participation will span 8 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 completing the arm of the IPC regimen to which he/she has been assigned.

Other results which may arise from the trial are:

* The tolerance of RIPC in rheumatology patients, by monitoring side-effects.
* The attitude of rheumatology patients in using non-pharmacological treatments, 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 fewer side-effects and be better accepted because it is a common and safe non-pharmacological intervention.

Eligibility criteria: Inclusion Criteria:

1. Primary or secondary RP, as diagnosed by a rheumatologist
2. Clinical need for treatment for RP
3. At least 7 RP attacks per week
4. Systolic blood pressure above 80mmHg
5. Willing to provide informed consent

Exclusion Criteria:

1. New or changed dose of drugs used for RP treatment in the last 2 weeks: calcium channel blockers, alpha1-adrenergic blockers, angiotensin II receptor antagonists, nitroglycerin, prostaglandins, pentoxifylline, endothelin antagonists and/or phosphodiesterase type 5 inhibitors.
2. Non-compliance with past therapies

Primary outcomes:
measure: Changes in frequency of RP attacks
timeFrame: Entire study duration (8 weeks including pretreatment and washout period)
measure: Changes in severity of RP attacks
timeFrame: Entire study duration (8 weeks including pretreatment and washout period)
measure: Changes in duration of RP attacks
timeFrame: Entire study duration (8 weeks including pretreatment and washout period)
Secondary outcomes:
measure: Functions questionnaires (Raynaud's Condition Score)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
measure: Biological marker of endothelial damage (P-selectin)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
measure: Biological marker of endothelial damage (I-CAM)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
measure: Biological marker of endothelial damage (VEGF)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
measure: Functions questionnaires (HAQ-DI)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
measure: Functions questionnaires (DASH)
timeFrame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Other outcomes:
Locations:
city: London
country: Canada
facility: Rheumatology Clinic, St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: Division of Rheumatology, Department of Medicine, Western University
name: Janet E Pope
role: PRINCIPAL_INVESTIGATOR
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