Allopurinol in Functional Impairment (ALFIE) Trial: 'Improving Muscle Strength'

Sponsor

University of Dundee (Other)

Overall Status

Completed

CT.gov ID

NCT01550107

Collaborator

(none)

124

Enrollment

Location

Arms

31.6

Actual Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Sarcopenia is defined as the presence of low muscle mass and either decreased muscle strength or function. It is increasingly becoming a significant cause of frailty, loss of independence and physical disability in ageing western populations. Recent experimental evidence has revealed that skeletal muscle is particularly susceptible to damaging molecules that result in oxidative stress and that oxidative stress plays a prominent role in the development and progression of sarcopenia. The investigators have previously shown that the xanthine oxidase inhibitor allopurinol is able to abolish vascular oxidative stress and improve endothelial function in cohorts such as optimally treated chronic heart failure and chronic kidney disease. Recently, the investigators have also shown that allopurinol improves exercise tolerance and time to ST-depression in optimally treated coronary artery disease, suggesting that allopurinol could also exert its effects through ATP and/or oxygen sparing mechanisms.

Therefore, we propose a randomised double blind placebo-controlled parallel group trial of allopurinol in patients with primary sarcopenia using MR-spectroscopy and Flow Mediated Dilatation to investigate the possible mechanisms that underlie this exciting possibility

Condition or Disease	Intervention/Treatment	Phase
Sarcopenia	Drug: Allopurinol Drug: Lactose tablets	Phase 4

Detailed Description

this section will be completed once the study is officially recruiting

Study Design

Study Type:

Interventional

Actual Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Prospective Study to Evaluate the Effect of Allopurinol on Muscle Energetics in Primary Sarcopenia

Actual Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Sep 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Allopurinol Allopurinol 600mg tablets	Drug: Allopurinol 300mg b.d for 24 weeks
Placebo Comparator: Lactose tablets Placebo Lactose tablets	Drug: Lactose tablets matched placebo tablets b.d

Arm

Intervention/Treatment

Active Comparator: Allopurinol

Allopurinol 600mg tablets

Drug: Allopurinol

300mg b.d for 24 weeks

Placebo Comparator: Lactose tablets

Placebo Lactose tablets

Drug: Lactose tablets

matched placebo tablets b.d

Outcome Measures

Primary Outcome Measures

Improvement in Muscle energetics as measured by MR-spectroscopy [24 weeks]
PCr repletion,Post-exercise muscle perfusion via arterial spin labelling (ASL) Pi/PCr ratio (a measure of ADP levels) Change in muscle volume (as measured by cross-sectional area on MR obtained during perfusion mapping)

Secondary Outcome Measures

Short Performance Battery test [24 weeks]
6-Minute Walk Test [24 weeks]
Change in Flow Mediated Dilatation [24 weeks]
Markers of oxidative stress (F2-Isoprostanes) [24 weeks]
Quality of Life measured by EuroQOL EQ5D questionnaire [24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 65 and over 6-Minute Walk Distance <400m

Exclusion Criteria:

Documented history of peripheral arterial disease. Pre-existing diagnosis of severe heart failure (LVEF<35%). Malignancy under active treatment (excluding basal cell carcinoma). Severe COPD (Physician diagnosis). Intolerance to allopurinol. Individuals with Active Acute Gout currently taking allopurinol; or those who have stopped taking allopurinol ≤1month previously for this condition.

On long term high dose steroids (eq. Prednisolone>10mg/day due to risk of steroid induced myopathy and osteoporosis).

Immobility that would render the patient incapable of doing the Short Physical Performance Battery Test (SPPB) or 6MWT.

Patients who have participated in any other clinical drug trial within the previous 30 days will be excluded.

Cognitive impairment precluding informed consent. Any other considered by a study physician to be inappropriate for inclusion.