Effects of Remote Ischemic Preconditioning on Moderate PVD Patients A Pilot Randomized Control Trial

NCT02273232 | Completed Phase 1 DMC

• 1 other identifier: C.A 1154
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Remote ischemic Preconditioning (RIPC) is a phenomena first observed in cardio-thoracic patients in which exposing the limbs for periods of short intermittent ischemia produces protective effect on heart muscle. The concept was applied to many other parts of the body and the results are positive so far. No human trials on this concept has been conducted in patients with peripheral vascular disease so far but applying the concept for healthy individuals shows vessels dilatation and animal trials shows degree of new vessels formation in addition to reports of symptoms improvement. The trial candidates will be allocated blindly in 4 groups. All groups will have advice about exercise which is the standard practice now. The first group will have supervised exercise. The second group will in addition to the supervised exercise get the ischemic preconditioning with the blood pressure cuff. The third group will get the ischemic preconditioning and the fourth group will get the standard exercise advice. All candidates will have Magnetic Resonance Image Scan (MRA) for their blood vessels in the beginning of the trial and again at the end. The effect of the RIPC (Remote ischemic Preconditioning) and exercises on patient symptoms, new vessel formation and other parameters will be recorded

Conditions

Peripheral Arterial Diseases

Keywords

Peripheral Arterial Disease; Peripheral Vascular Disease; Claudication; Remote Ischemic Preconditioning; EQ-5D; Symptoms free distance; ABI; micro vessel formation

Outcome Measures

Primary Outcomes (4)

• Symptoms free distance

  Distance which patient can walk without pain at the beginning and the end of the trial will be compared and compared cross groups

  30 days

• ABI -Ankle-Brachial Index Test

  ABI measured at the beginning and the end of the trial comparing pre and post results in all groups will be analysed

  30 days

• 6-minute walk test

  The standard Test (american college of rheumatology) results will be measured pre and post trial to evaluate any change in functional exercise capacity

  30 days

• EQ-5D quality of life measures

  EQ-5D questionnaire will be used as slandered Quality of life assessment tool post trial for candidates a cross groups - http://www.euroqol.org/

  6 months

Secondary Outcomes (5)

• Effects on BP (Blood Pressure )

  30 days

• % changes in ABI

  30 days

• Minor amputations

  30 days

• Progress for amputation during trial

  30 days

• Progression of Rutherford classification

  30 days

Study Arms (4)

Supervised Exercise Group

ACTIVE COMPARATOR

All PVD patients will get the standard advice regarding exercises but this group will have a constructed exercise program under supervision of Dr. Micheál Newell who is qualified Sports and Exercise Scientist with a Doctorate degree in Integrated Biology. This include six minute walk test, Chair Stand Test and symptoms free distance.

Other: Supervised Exercise; Other: Standard Care

RIPC and supervised Exercise Group

ACTIVE COMPARATOR

This group will have structured intermitting periods of induced remote ischaemic preconditioning using standard blood pressure cuffs. The cuff will be applied for 5 minutes alternatively with 5 minutes rest to the total of 4 cycles, which needs 40 minutes per day. The RIPC group will receive an exercise program identical to the first group. The total number of days for each participant will be 28 days.

Other: Remote Ischemic Preconditioning; Other: Supervised Exercise; Other: Standard Care

RIPC with Standard Care Group

ACTIVE COMPARATOR

The patients in this group will receive standard care advice regarding exercise in addition to RIPC as in the 2nd group.

Other: Remote Ischemic Preconditioning; Other: Standard Care

Control Group (Standard Care)

SHAM COMPARATOR

This group will get the standard advice regarding exercise for PVD patients and all the information available in Out patients clinic settings.

Other: Standard Care

Interventions

Remote Ischemic Preconditioning OTHER

Blood pressure cuff will be inflated to 200 mmhg for 5 minuets and release for 5 minuets to total of 4 cycles

Also known as: RIPC

RIPC and supervised Exercise Group; RIPC with Standard Care Group

Supervised Exercise OTHER

constructed extra excessive for peripheral vascular diastase patients

RIPC and supervised Exercise Group; Supervised Exercise Group

Standard Care OTHER

Standard Care for peripheral vascular disease patients including advises regarding exercises

Control Group (Standard Care); RIPC and supervised Exercise Group; RIPC with Standard Care Group; Supervised Exercise Group

Eligibility Criteria

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

You may qualify if:

• Known moderate PVD
• New claudication patient with Rutherford stage 2 and Fontaine stage 2a symptoms

You may not qualify if:

• Known upper limb PVD
• Severe cardiac condition
• Risk classification for exercise training: class C and above
• Severe respiratory condition
• Previous history of upper limb deep vein thrombosis
• Patients on glibenclamide or nicorandil- May affect RIPC
• Raynaud's Disease
• Contra indications for MRA
• Pregnancy
• Previous major limb amputation affect ability to exercise

Sponsors & Collaborators

• National University of Ireland, Galway, Ireland: lead
• University College Hospital Galway: collaborator

Study Sites (1)

University Collage Hospital Galway

Galway, Co Galway, Ireland

Location

Related Publications (16)

• Andreozzi GM, Leone A, Laudani R, Deinite G, Martini R. Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training. Int Angiol. 2007 Mar;26(1):12-7.

  PMID: 17353883 RESULT

• Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation. 1997 Sep 2;96(5):1641-6. doi: 10.1161/01.cir.96.5.1641.

  PMID: 9315559 RESULT

• Capecchi PL, Pasini FL, Cati G, Colafati M, Acciavatti A, Ceccatelli L, Petri S, de Lalla A, Di Perri T. Experimental model of short-time exercise-induced preconditioning in POAD patients. Angiology. 1997 Jun;48(6):469-80. doi: 10.1177/000331979704800601.

  PMID: 9194532 RESULT

• Dickson EW, Porcaro WA, Fenton RA, Heard SO, Reindhardt CP, Renzi FP, Przyklenk K. "Preconditioning at a distance" in the isolated rabbit heart. Acad Emerg Med. 2000 Apr;7(4):311-7. doi: 10.1111/j.1553-2712.2000.tb02228.x.

  PMID: 10805617 RESULT

• Dormandy J, Heeck L, Vig S. Intermittent claudication: a condition with underrated risks. Semin Vasc Surg. 1999 Jun;12(2):96-108.

  PMID: 10777236 RESULT

• Enko K, Nakamura K, Yunoki K, Miyoshi T, Akagi S, Yoshida M, Toh N, Sangawa M, Nishii N, Nagase S, Kohno K, Morita H, Kusano KF, Ito H. Intermittent arm ischemia induces vasodilatation of the contralateral upper limb. J Physiol Sci. 2011 Nov;61(6):507-13. doi: 10.1007/s12576-011-0172-9. Epub 2011 Sep 8.

  PMID: 21901641 RESULT

• Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001 Oct 2;104(14):1694-740. doi: 10.1161/hc3901.095960. No abstract available.

  PMID: 11581152 RESULT

• Fowkes FG, Housley E, Cawood EH, Macintyre CC, Ruckley CV, Prescott RJ. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1991 Jun;20(2):384-92. doi: 10.1093/ije/20.2.384.

  PMID: 1917239 RESULT

• Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006 Feb 1;295(5):547-53. doi: 10.1001/jama.295.5.547.

  PMID: 16449620 RESULT

• Karakoyun R, Koksoy C, Yilmaz TU, Altun H, Banli O, Albayrak A, Alper M, Sener Z. The angiogenic effects of ischemic conditioning in experimental critical limb ischemia. Eur J Vasc Endovasc Surg. 2014 Feb;47(2):172-9. doi: 10.1016/j.ejvs.2013.11.001. Epub 2013 Nov 11.

  PMID: 24333045 RESULT

• Layden J, Michaels J, Bermingham S, Higgins B; Guideline Development Group. Diagnosis and management of lower limb peripheral arterial disease: summary of NICE guidance. BMJ. 2012 Aug 8;345:e4947. doi: 10.1136/bmj.e4947. No abstract available.

  PMID: 22875949 RESULT

• Mahoney EM, Wang K, Keo HH, Duval S, Smolderen KG, Cohen DJ, Steg G, Bhatt DL, Hirsch AT; Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):642-51. doi: 10.1161/CIRCOUTCOMES.109.930735. Epub 2010 Oct 12.

  PMID: 20940249 RESULT

• Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124-36. doi: 10.1161/01.cir.74.5.1124.

  PMID: 3769170 RESULT

• Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007 Jan;45 Suppl S:S5-67. doi: 10.1016/j.jvs.2006.12.037. No abstract available.

  PMID: 17223489 RESULT

• Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.

  PMID: 7680290 RESULT

• Walsh SR, Tang TY, Kullar P, Jenkins DP, Dutka DP, Gaunt ME. Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur J Cardiothorac Surg. 2008 Nov;34(5):985-94. doi: 10.1016/j.ejcts.2008.07.062. Epub 2008 Sep 9.

  PMID: 18783958 RESULT

MeSH Terms

Conditions

Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Stewart E Walsh, Professor

  NUIG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr/Mr

Study Record Dates

• First Submitted: October 18, 2014
• First Posted: October 23, 2014
• Study Start: January 1, 2015
• Primary Completion: May 5, 2017
• Study Completion: May 5, 2017
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

IE (1)