A Trial of Ischemic Preconditioning in Raynaud's Phenomenon (RP)
Condition: Raynaud Disease; Raynaud's Phenomenon
MeSH terms: Raynaud Disease
Study type: Interventional

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.
    

Intervention name(s): Manual blood pressure cuff inflation over brachial artery
Intervention type(s): Device
Intervention description(s): A manual blood pressure cuff (sphygmomanometer) is used in the study as a tourniquet in order to perform a controlled, consistent level of ischemia (200mmHg/active arm or 60 mmHg/placebo arm).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: ischemic preconditioning; Raynaud's Phenomenon; (RP)