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

• ClinicalTrials.gov Identifier: NCT01550107
• Recruitment Status: Completed
• First Posted: March 9, 2012
• Last Update Posted: March 20, 2018
• Sponsor: University of Dundee
• Information provided by (Responsible Party): Dr. Jacob George, University of Dundee

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 (Clinical Trial)
• 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: February 1, 2015
• Actual Primary Completion Date: August 1, 2017
• Actual Study Completion Date: September 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

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. Short Performance Battery test [ Time Frame: 24 weeks ]
2. 6-Minute Walk Test [ Time Frame: 24 weeks ]
3. Change in Flow Mediated Dilatation [ Time Frame: 24 weeks ]
4. Markers of oxidative stress (F2-Isoprostanes) [ Time Frame: 24 weeks ]
5. Quality of Life measured by EuroQOL EQ5D questionnaire [ Time Frame: 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Dr. Jacob George, Chief Investigator, University of Dundee
• ClinicalTrials.gov Identifier: NCT01550107 History of Changes
• Other Study ID Numbers: GEO006
• First Posted: March 9, 2012
• Last Update Posted: March 20, 2018
• Last Verified: March 2018

Keywords provided by Dr. Jacob George, 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