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

NCT01550107 | Completed Phase 4

• 1 other identifier: GEO006
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

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

Conditions

Sarcopenia

Keywords

Sarcopenia; Allopurinol; Xanthine Oxidase; MR Spectroscopy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

Allopurinol 600mg tablets

Drug: Allopurinol

Lactose tablets

PLACEBO COMPARATOR

Placebo Lactose tablets

Drug: Lactose tablets

Interventions

Allopurinol DRUG

300mg b.d for 24 weeks

Allopurinol

Lactose tablets DRUG

matched placebo tablets b.d

Lactose tablets

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65 and over 6-Minute Walk Distance \<400m

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

University of Dundee Medical School

Dundee, Angus, DD1 9SY, United Kingdom

Location

MeSH Terms

Conditions

Sarcopenia

Interventions

Allopurinol; Lactose

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Jacob George, MRCP MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

• Clare Clarke, PhD MCSP

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: March 9, 2012
• Study Start: February 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: September 20, 2017
• Last Updated: March 20, 2018

Record last verified: 2018-03

Locations

GB (1)