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

Primary Purpose

Raynaud Disease, Raynaud's Phenomenon

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Manual blood pressure cuff inflation over brachial artery
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Raynaud Disease focused on measuring ischemic preconditioning, Raynaud's Phenomenon, (RP)

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Rheumatology Clinic, St. Joseph's Health Care

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active Arm - 200 mmHg

Placebo Arm - 60 mmHg

Arm 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.

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.

Outcomes

Primary Outcome Measures

Changes in frequency of RP attacks
The subject will self-assess the number of RP attacks daily in their RP diary.
Changes in severity of RP attacks
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).
Changes in duration of RP attacks
The subject will self-assess the duration (in minutes) of RP attacks daily in their RP diary.

Secondary Outcome Measures

Functions questionnaires (Raynaud's Condition Score)
Biological marker of endothelial damage (P-selectin)
Biological marker of endothelial damage (I-CAM)
Biological marker of endothelial damage (VEGF)
Functions questionnaires (HAQ-DI)
Health Assessment Questionnaire - Disability Index
Functions questionnaires (DASH)
Disabilities of the Arm, Shoulder, and Hand

Full Information

First Posted
July 8, 2015
Last Updated
August 7, 2018
Sponsor
Lawson Health Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02506062
Brief Title
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
August 2018 (Actual)
Study Completion Date
August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lawson Health Research Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Raynaud Disease, Raynaud's Phenomenon
Keywords
ischemic preconditioning, Raynaud's Phenomenon, (RP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active Arm - 200 mmHg
Arm Type
Experimental
Arm 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.
Arm Title
Placebo Arm - 60 mmHg
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Device
Intervention Name(s)
Manual blood pressure cuff inflation over brachial artery
Intervention Description
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).
Primary Outcome Measure Information:
Title
Changes in frequency of RP attacks
Description
The subject will self-assess the number of RP attacks daily in their RP diary.
Time Frame
Entire study duration (8 weeks including pretreatment and washout period)
Title
Changes in severity of RP attacks
Description
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).
Time Frame
Entire study duration (8 weeks including pretreatment and washout period)
Title
Changes in duration of RP attacks
Description
The subject will self-assess the duration (in minutes) of RP attacks daily in their RP diary.
Time Frame
Entire study duration (8 weeks including pretreatment and washout period)
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
Functions questionnaires (HAQ-DI)
Description
Health Assessment Questionnaire - Disability Index
Time Frame
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks
Title
Functions questionnaires (DASH)
Description
Disabilities of the Arm, Shoulder, and Hand
Time Frame
Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Primary or secondary RP, as diagnosed by a rheumatologist Clinical need for treatment for RP At least 7 RP attacks per week Systolic blood pressure above 80mmHg Willing to provide informed consent Exclusion Criteria: 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. Non-compliance with past therapies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet E Pope
Organizational Affiliation
Division of Rheumatology, Department of Medicine, Western University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rheumatology Clinic, St. Joseph's Health Care
City
London
State/Province
Ontario
Country
Canada

12. IPD Sharing Statement

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Links:
URL
http://www.niams.nih.gov/Health_Info/Raynauds_Phenomenon/default.asp
Description
American website of institute of arthritis: general medical information on Raynaud's Disease
URL
http://www.raynauds.org.uk
Description
British site for Raynaud's patients: cover medical data as well as support programs

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

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