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

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
Dr. Jacob George, University of Dundee Identifier:
First received: March 7, 2012
Last updated: December 1, 2015
Last verified: December 2015

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 Intervention Phase
Drug: Allopurinol
Drug: Lactose tablets
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Study to Evaluate the Effect of Allopurinol on Muscle Energetics in Primary Sarcopenia

Resource links provided by NLM:

Further study details as provided by University of Dundee:

Primary Outcome Measures:
  • Improvement in Muscle energetics as measured by MR-spectroscopy [ Time Frame: 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 [ Time Frame: 24 weeks ]
  • 6-Minute Walk Test [ Time Frame: 24 weeks ]
  • Change in Flow Mediated Dilatation [ Time Frame: 24 weeks ]
  • Markers of oxidative stress (F2-Isoprostanes) [ Time Frame: 24 weeks ]
  • Quality of Life measured by EuroQOL EQ5D questionnaire [ Time Frame: 24 weeks ]

Estimated Enrollment: 124
Study Start Date: December 2014
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:
this section will be completed once the study is officially recruiting

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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Please refer to this study by its identifier: NCT01550107

United Kingdom
University of Dundee Medical School
Dundee, Angus, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
Principal Investigator: Jacob George, MRCP MD University of Dundee
Study Director: Allan Struthers, MD FRCP 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
  More Information

Responsible Party: Dr. Jacob George, Chief Investigator, University of Dundee Identifier: NCT01550107     History of Changes
Other Study ID Numbers: GEO006
Study First Received: March 7, 2012
Last Updated: December 1, 2015

Keywords provided by University of Dundee:
Xanthine Oxidase
MR Spectroscopy

Additional relevant MeSH terms:
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathological Conditions, Anatomical
Signs and Symptoms
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Protective Agents
Physiological Effects of Drugs processed this record on April 25, 2017