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

August 7, 2018 updated by: Janet Pope, Lawson Health Research Institute

A Randomized, Single-blinded Placebo-controlled Trial of Ischemic Preconditioning in Raynaud's Phenomenon (RP)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada
        • Rheumatology Clinic, St. Joseph's Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active Arm - 200 mmHg
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.
Device: Manual blood pressure cuff inflation over brachial artery
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).
Placebo Comparator: Placebo Arm - 60 mmHg
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.
Device: Manual blood pressure cuff inflation over brachial artery
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in frequency of RP attacks
Time Frame: Entire study duration (8 weeks including pretreatment and washout period)
The subject will self-assess the number of RP attacks daily in their RP diary.
Entire study duration (8 weeks including pretreatment and washout period)
Changes in severity of RP attacks
Time Frame: Entire study duration (8 weeks including pretreatment and washout period)
Severity will be evaluated on a scale of 1 to 10. The subject will self-assess the severity in their RP diary. (0 = no difficulty with RP condition, 10 = extreme difficulty with RP condition).
Entire study duration (8 weeks including pretreatment and washout period)
Changes in duration of RP attacks
Time Frame: Entire study duration (8 weeks including pretreatment and washout period)
The subject will self-assess the duration (in minutes) of RP attacks daily in their RP diary.
Entire study duration (8 weeks including pretreatment and washout period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functions questionnaires (Raynaud's Condition Score)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Biological marker of endothelial damage (P-selectin)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Biological marker of endothelial damage (I-CAM)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Biological marker of endothelial damage (VEGF)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Functions questionnaires (HAQ-DI)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Health Assessment Questionnaire - Disability Index
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Functions questionnaires (DASH)
Time Frame: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Disabilities of the Arm, Shoulder, and Hand
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Janet E Pope, Division of Rheumatology, Department of Medicine, Western University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

August 1, 2018

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

July 8, 2015

First Submitted That Met QC Criteria

July 21, 2015

First Posted (Estimate)

July 22, 2015

Study Record Updates

Last Update Posted (Actual)

August 8, 2018

Last Update Submitted That Met QC Criteria

August 7, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 106798

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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