Allopurinol in Functional Impairment (ALFIE) Trial: 'Improving Muscle Strength'
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Purpose
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 |
|---|---|---|
|
Sarcopenia |
Drug: Allopurinol Drug: Lactose tablets |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Prospective Study to Evaluate the Effect of Allopurinol on Muscle Energetics in Primary Sarcopenia |
- Improvement in Muscle energetics as measured by MR-spectroscopy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]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)
- Short Performance Battery test [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- 6-Minute Walk Test [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change in Flow Mediated Dilatation [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Markers of oxidative stress (F2-Isoprostanes) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Quality of Life measured by EuroQOL EQ5D questionnaire [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
| 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:
Eligibility| Ages Eligible for Study: | 65 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| 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.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01550107
| United Kingdom | |
| University of Dundee Medical School | |
| Dundee, Angus, United Kingdom, DD1 9SY | |
| 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 |
| ClinicalTrials.gov Identifier: | NCT01550107 History of Changes |
| Other Study ID Numbers: | GEO006 |
| Study First Received: | March 7, 2012 |
| Last Updated: | December 1, 2015 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by University of Dundee:
|
Sarcopenia Allopurinol Xanthine Oxidase MR Spectroscopy |
Additional relevant MeSH terms:
|
Sarcopenia Muscular Atrophy Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases Atrophy Pathological Conditions, Anatomical Signs and Symptoms Allopurinol |
Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Gout Suppressants Antirheumatic Agents Free Radical Scavengers Antioxidants Protective Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 27, 2016