A Trial of Ischemic Preconditioning in Raynaud's Phenomenon (RP)

Lawson Health Research Institute

Status: Completed

Conditions: Raynaud's Phenomenon; Raynaud Disease

Treatments: Device: Manual blood pressure cuff inflation over brachial artery

Study type: Interventional

Funder types: Other

Identifiers

NCT02506062

106798

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 69 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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21 participants in 2 patient groups, including a placebo group

Active Arm - 200 mmHg

Experimental group

Description:

Patients who start in the active arm of the study will receive ischemic preconditioning (IPC) treatment consisting of applying the blood pressure cuff to a pressure of 200 mmHg for 2 minutes and thirty seconds with a resting period of two minutes and thirty seconds between treatments. This procedure is performed four times, for a total of twenty minutes per treatment. This treatment will be done three times a week. Patients may choose to treat at home with a portable manual blood pressure machine or may be treated in clinic by research staff. Patients will receive treatment for two weeks followed by a wash-out period (no treatment) of two weeks. Patients will then receive the placebo treatment. This completes their participation in the study.

Treatment:

Device: Manual blood pressure cuff inflation over brachial artery

Placebo Arm - 60 mmHg

Placebo Comparator group

Description:

Patients who start in the placebo arm will receive placebo treatment, consisting of applying the blood pressure cuff to a pressure of 60 mmHg for 2 minutes and thirty seconds with a resting period of two minutes and thirty seconds between treatments. This procedure is performed four times, for a total of twenty minutes per treatment. This treatment will be done three times a week for two weeks followed by a two week wash-out and then two weeks in the active treatment phase, thus completing their participation in the study.

Treatment:

Device: Manual blood pressure cuff inflation over brachial artery