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

NCT02506062 | Completed

• 1 other identifier: 106798
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Raynaud Disease; Raynaud's Phenomenon

Keywords

ischemic preconditioning; Raynaud's Phenomenon; (RP)

Outcome Measures

Primary Outcomes (3)

• Changes in frequency of RP attacks

  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

  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

  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 Outcomes (6)

• Functions questionnaires (Raynaud's Condition Score)

  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)

  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)

  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)

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

• Functions questionnaires (HAQ-DI)

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

Study Arms (2)

Active Arm - 200 mmHg

EXPERIMENTAL

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

Placebo Arm - 60 mmHg

PLACEBO COMPARATOR

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

Interventions

Manual blood pressure cuff inflation over brachial artery DEVICE

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).

Active Arm - 200 mmHg; Placebo Arm - 60 mmHg

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Rheumatology Clinic, St. Joseph's Health Care

London, Ontario, Canada

Location

Related Publications (22)

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

  PMID: 24112969 BACKGROUND

• 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.

  PMID: 17352512 BACKGROUND

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

  PMID: 10218222 BACKGROUND

• 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.

  PMID: 15546967 BACKGROUND

• 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.

  PMID: 19376531 BACKGROUND

• 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.

  PMID: 21300953 BACKGROUND

• 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.

  PMID: 19040966 BACKGROUND

• 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.

  PMID: 21398019 BACKGROUND

• 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.

  PMID: 20850778 BACKGROUND

• 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.

  PMID: 8124814 BACKGROUND

• 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.

  PMID: 11273988 BACKGROUND

• 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.

  PMID: 10600871 BACKGROUND

• 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.

  PMID: 10430769 BACKGROUND

• 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.

  PMID: 24627443 BACKGROUND

• 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.

  PMID: 17446439 BACKGROUND

• Vasdekis SN, Athanasiadis D, Lazaris A, Martikos G, Katsanos AH, Tsivgoulis G, Machairas A, Liakakos T. The role of remote ischemic preconditioning in the treatment of atherosclerotic diseases. Brain Behav. 2013 Nov;3(6):606-16. doi: 10.1002/brb3.161. Epub 2013 Aug 30.

  PMID: 24363964 BACKGROUND

• Alreja G, Bugano D, Lotfi A. Effect of remote ischemic preconditioning on myocardial and renal injury: meta-analysis of randomized controlled trials. J Invasive Cardiol. 2012 Feb;24(2):42-8.

  PMID: 22294530 BACKGROUND

• Pilcher JM, Young P, Weatherall M, Rahman I, Bonser RS, Beasley RW. A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery. J R Soc Med. 2012 Oct;105(10):436-45. doi: 10.1258/jrsm.2012.120049.

  PMID: 23104947 BACKGROUND

• Brevoord D, Kranke P, Kuijpers M, Weber N, Hollmann M, Preckel B. Remote ischemic conditioning to protect against ischemia-reperfusion injury: a systematic review and meta-analysis. PLoS One. 2012;7(7):e42179. doi: 10.1371/journal.pone.0042179. Epub 2012 Jul 31.

  PMID: 22860077 BACKGROUND

• Li C, Li YS, Xu M, Wen SH, Yao X, Wu Y, Huang CY, Huang WQ, Liu KX. Limb remote ischemic preconditioning for intestinal and pulmonary protection during elective open infrarenal abdominal aortic aneurysm repair: a randomized controlled trial. Anesthesiology. 2013 Apr;118(4):842-52. doi: 10.1097/ALN.0b013e3182850da5.

  PMID: 23353795 BACKGROUND

• Koch S, Katsnelson M, Dong C, Perez-Pinzon M. Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase Ib study of safety and feasibility. Stroke. 2011 May;42(5):1387-91. doi: 10.1161/STROKEAHA.110.605840. Epub 2011 Mar 17.

  PMID: 21415404 BACKGROUND

• Luca MC, Liuni A, McLaughlin K, Gori T, Parker JD. Daily ischemic preconditioning provides sustained protection from ischemia-reperfusion induced endothelial dysfunction: a human study. J Am Heart Assoc. 2013 Feb 22;2(1):e000075. doi: 10.1161/JAHA.112.000075.

  PMID: 23525419 BACKGROUND

Related Links

• American website of institute of arthritis: general medical information on Raynaud's Disease

MeSH Terms

Conditions

Raynaud Disease

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Janet E Pope

  Division of Rheumatology, Department of Medicine, Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 22, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 8, 2018

Record last verified: 2018-08

Locations

CA (1)