Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease

NCT01147705 | Completed Phase 4

• 2 other identifiers: 2009CV162010-020662-23
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral arterial disease (PAD) is a common condition that arises due to the build up of atheroma in the arteries supplying blood to the peripheral muscles and other tissues. This imbalance between oxygen supply and demand becomes particularly apparent when patients with the condition are walking. The pain and weakness they experience (mainly in the calf but less commonly in the thigh) is known as intermittent claudication and resolves upon cessation of exercise. It is an important disease to study as it is (i) common (est. prevalence of symptomatic intermittent claudication in Scotland of 4.5%) and (ii) those with it have a 1.6 times higher relative risk of ischaemic heart disease. These patients also have a significantly higher mortality than age-matched controls at around 12% per year. There are two main aims of therapy - (i) to reduce the risk of cardiovascular events by way of standard secondary prevention measures (smoking cessation, anti-platelet, anti-hypertensive and cholesterol-lowering therapy, diabetic control) and (ii) to treat symptoms. Supervised exercise therapy has been shown to be beneficial in improving walking time and distance in selected patients with leg pain from intermittent claudication with an overall increase in walking distance of approximately 150 metres at three months. There are numerous drug treatments available for consideration in PAD patients (mainly cilostazol in the UK), but many of these have either undesirable side effects or no clear evidence of benefit. The range of increase in walking distance on cilostazol was reported to be a 50-76% increase over three months compared to 20% with placebo with some significant improvements in Quality of Life (QOL) indicators, although with a significant number of adverse effects (16% vs 8% on placebo) limiting therapy. The current cost (March 2010) is £35.31/month. Other options for therapy include angioplasty and bypass surgery. At present these are only recommended for patients who fail to respond to medical therapy and have severely disabling symptoms (in the absence of significant exercise-limiting comorbidities).

Conditions

Peripheral Arterial Disease

Keywords

Peripheral arterial disease; Allopurinol

Outcome Measures

Primary Outcomes (1)

• Onset of claudication pain

  Our primary endpoint will be the distance to onset of claudication pain at 24 weeks but we will also measure total exercise distance.

  24 weeks

Secondary Outcomes (2)

• Quality of life

  24 weeks

• Anti-oxidant effects

  24 weeks

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

Participants will be given blinded medication and asked to take one tab/day for the first six weeks (100mg strength for two weeks then 300mg strength for four weeks) followed by two tabs/day for the remaining 18 weeks.

Drug: Allopurinol

Placebo

PLACEBO COMPARATOR

Same number of tablets and appearance as active drug.

Drug: Placebo

Interventions

Allopurinol DRUG

Participants will be given blinded medication and asked to take one tab/day for the first six weeks (100mg strength for two weeks then 300mg strength for four weeks) followed by two tabs/day for the remaining 18 weeks

Allopurinol

Placebo DRUG

Same appearance/dosing as active drug.

Placebo

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- stable peripheral arterial disease (demonstrated by having a reproducible pain free walking distance on 2 consecutive treadmill tests, i.e. less than 25% variance with the reason for termination of the treadmill test must be claudication pain only)

You may not qualify if:

• rest pain
• childbearing potential
• heart failure
• any other exercise limiting cardiac disease
• BP \> 180/100 mHg
• eGFR \< 60 ml/min
• liver disease
• malignancy
• already on allopurinol or had an adverse reaction to it
• recent marked change in symptoms or recent (in the last six months) intervention for PAD
• receiving treatment with either 6-mercaptopurine, azathioprine, warfarin, or theophylline

Sponsors & Collaborators

• University of Dundee: lead
• NHS Tayside: collaborator
• British Heart Foundation: collaborator

Study Sites (1)

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (1)

• Robertson AJ, Struthers AD. A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease. Can J Cardiol. 2016 Feb;32(2):190-6. doi: 10.1016/j.cjca.2015.05.010. Epub 2015 May 19.

  PMID: 26277090 RESULT

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Allan Struthers, MD FRCP

  University of Dundee

  STUDY DIRECTOR

• Alan J Robertson, MBChB MRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Fellow

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 22, 2010
• Study Start: February 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 2, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)