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

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

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

Study Overview

• Status: Completed
• Conditions: Sarcopenia
• Intervention / Treatment: Drug: Allopurinol; Drug: Lactose tablets

Detailed Description

this section will be completed once the study is officially recruiting

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • University of Dundee Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Muscle energetics as measured by MR-spectroscopy	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)	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Dundee
• Investigators: Principal Investigator: Jacob George, MRCP MD, University of Dundee; Study Director: Marion McMurdo, MD FRCP, University of Dundee; Study Director: Miles Witham, PhD FRCP, University of Dundee; Study Director: Graeme Houston, FRCP FRCR, University of Dundee; Study Director: Steve Gandy, PhD, University of Dundee; Study Director: Peter Donnan, PhD FRSS, University of Dundee; Principal Investigator: Clare Clarke, PhD MCSP, University of Dundee

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2015
• Primary Completion (ACTUAL): August 1, 2017
• Study Completion (ACTUAL): September 20, 2017

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (ESTIMATE): March 9, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2018
• Last Update Submitted That Met QC Criteria: March 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Sarcopenia; Allopurinol; MR Spectroscopy; Xanthine Oxidase
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: GEO006