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Raynaud DiseaseNCT02506062

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

A study testing Manual blood pressure cuff inflation over brachial artery in people with Raynaud Disease and Raynaud's Phenomenon, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Raynaud Disease, Raynaud's Phenomenon
What is being tested?
Manual blood pressure cuff inflation over brachial artery
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
1 siteCanada
Study dates
Jul 2015to Aug 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Rheumatology Clinic, St. Joseph's Health Care

    London, Ontario

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
Manual blood pressure cuff inflation over brachial artery
Keywords
ischemic preconditioning, Raynaud's Phenomenon, (RP)
Medical subject headings
Raynaud Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Manual blood pressure cuff inflation over brachial arteryDevice

    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).

Study groups in NCT02506062
Study groupRoleWhat they receive
Active Arm - 200 mmHgExperimentalPatients 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.
Receives: Device: Manual blood pressure cuff inflation over brachial artery
Placebo Arm - 60 mmHgPlacebo comparatorPatients 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.
Receives: Device: Manual blood pressure cuff inflation over brachial artery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in frequency of RP attacks

    The subject will self-assess the number of RP attacks daily in their RP diary.

    Measured: Entire study duration (8 weeks including pretreatment and washout period)

  2. 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).

    Measured: Entire study duration (8 weeks including pretreatment and washout period)

  3. Changes in duration of RP attacks

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

    Measured: Entire study duration (8 weeks including pretreatment and washout period)

Secondary outcomes (6)
  1. Functions questionnaires (Raynaud's Condition Score)

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

  2. Biological marker of endothelial damage (P-selectin)

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

  3. Biological marker of endothelial damage (I-CAM)

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

  4. Biological marker of endothelial damage (VEGF)

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

  5. Functions questionnaires (HAQ-DI)

    Health Assessment Questionnaire - Disability Index

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

  6. Functions questionnaires (DASH)

    Disabilities of the Arm, Shoulder, and Hand

    Measured: Every 2 weeks at clinic visits (baseline, after intervention, after washout, and after placebo) for a total of 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2015 (estimated)
  2. Study startJul 2015
  3. Primary completionAug 2018
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02506062
Sponsor's protocol ID
106798
Status last verified
Aug 2018
First submitted
8 Jul 2015
Last updated
8 Aug 2018
Results posted
No
Data monitoring committee
No

Publications

  • Pope J. Raynaud's phenomenon (primary). BMJ Clin Evid. 2013 Oct 10;2013:1119.

    PubMed 24112969
  • Pope JE. The diagnosis and treatment of Raynaud's phenomenon: a practical approach. Drugs. 2007;67(4):517-25. doi: 10.2165/00003495-200767040-00003.

    PubMed 17352512
  • Khan F. Vascular abnormalities in Raynaud's phenomenon. Scott Med J. 1999 Feb;44(1):4-6. doi: 10.1177/003693309904400102. No abstract available.

    PubMed 10218222
  • Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology (Oxford). 2005 Feb;44(2):145-50. doi: 10.1093/rheumatology/keh390. Epub 2004 Nov 16.

    PubMed 15546967
  • Lazaris AM, Maheras AN, Vasdekis SN, Karkaletsis KG, Charalambopoulos A, Kakisis JD, Martikos G, Patapis P, Giamarellos-Bourboulis EJ, Karatzas GM, Liakakos TD. Protective effect of remote ischemic preconditioning in renal ischemia/reperfusion injury, in a model of thoracoabdominal aorta approach. J Surg Res. 2009 Jun 15;154(2):267-73. doi: 10.1016/j.jss.2008.06.037. Epub 2008 Jul 26.

    PubMed 19376531
  • Jensen HA, Loukogeorgakis S, Yannopoulos F, Rimpilainen E, Petzold A, Tuominen H, Lepola P, Macallister RJ, Deanfield JE, Makela T, Alestalo K, Kiviluoma K, Anttila V, Tsang V, Juvonen T. Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation. 2011 Feb 22;123(7):714-21. doi: 10.1161/CIRCULATIONAHA.110.986497. Epub 2011 Feb 7.

    PubMed 21300953
  • Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review. J Surg Res. 2008 Dec;150(2):304-30. doi: 10.1016/j.jss.2007.12.747. Epub 2008 Jan 22.

    PubMed 19040966
  • Jan WC, Chen CH, Tsai PS, Huang CJ. Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shock/resuscitation in rats. Resuscitation. 2011 Jun;82(6):760-6. doi: 10.1016/j.resuscitation.2011.02.010. Epub 2011 Mar 12.

    PubMed 21398019
  • Li L, Luo W, Huang L, Zhang W, Gao Y, Jiang H, Zhang C, Long L, Chen S. Remote perconditioning reduces myocardial injury in adult valve replacement: a randomized controlled trial. J Surg Res. 2010 Nov;164(1):e21-6. doi: 10.1016/j.jss.2010.06.016. Epub 2010 Jul 2.

    PubMed 20850778
  • Richard V, Kaeffer N, Tron C, Thuillez C. Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation. 1994 Mar;89(3):1254-61. doi: 10.1161/01.cir.89.3.1254.

    PubMed 8124814
  • Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.

    PubMed 11273988
  • Davis JM, Gute DC, Jones S, Krsmanovic A, Korthuis RJ. Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine. Am J Physiol. 1999 Dec;277(6):H2476-81. doi: 10.1152/ajpheart.1999.277.6.H2476.

    PubMed 10600871
  • Beauchamp P, Richard V, Tamion F, Lallemand F, Lebreton JP, Vaudry H, Daveau M, Thuillez C. Protective effects of preconditioning in cultured rat endothelial cells: effects on neutrophil adhesion and expression of ICAM-1 after anoxia and reoxygenation. Circulation. 1999 Aug 3;100(5):541-6. doi: 10.1161/01.cir.100.5.541.

    PubMed 10430769
  • Jones H, Hopkins N, Bailey TG, Green DJ, Cable NT, Thijssen DH. Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans. Am J Hypertens. 2014 Jul;27(7):918-25. doi: 10.1093/ajh/hpu004. Epub 2014 Mar 13.

    PubMed 24627443
  • Kimura M, Ueda K, Goto C, Jitsuiki D, Nishioka K, Umemura T, Noma K, Yoshizumi M, Chayama K, Higashi Y. Repetition of ischemic preconditioning augments endothelium-dependent vasodilation in humans: role of endothelium-derived nitric oxide and endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1403-10. doi: 10.1161/ATVBAHA.107.143578. Epub 2007 Apr 19.

    PubMed 17446439

Questions about this trial

What is this clinical trial studying?

A study testing Manual blood pressure cuff inflation over brachial artery in people with Raynaud Disease and Raynaud's Phenomenon, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in frequency of RP attacks (time frame: Entire study duration (8 weeks including pretreatment and washout period)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02506062, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2018.

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