Allopurinol in Functional Impairment (ALFIE) Trial: 'Improving Muscle Strength' - Full Text View

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

Resource links provided by NLM:

Drug Information available for: Allopurinol Allopurinol sodium

U.S. FDA Resources

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 ] [ 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)

Secondary Outcome Measures:

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:

this section will be completed once the study is officially recruiting

Eligibility


Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01550107

Locations


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

Sponsors and Collaborators

University of Dundee

Investigators


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

No publications provided


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:	November 10, 2014
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 Atrophy Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathological Conditions, Anatomical Signs and Symptoms Allopurinol Antimetabolites	Antioxidants Antirheumatic Agents Enzyme Inhibitors Free Radical Scavengers Gout Suppressants Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protective Agents Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015