Clinical trial NCT01550107: Allopurinol in Functional Impairment (ALFIE) Trial: 'Improving Muscle Strength'
Official title: A Prospective Study to Evaluate the Effect of Allopurinol on Muscle Energetics in Primary Sarcopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sarcopenia
Keywords: Sarcopenia
Allopurinol
Xanthine Oxidase
MR Spectroscopy
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2012-03-09
Enrollment: 124
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility 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.

Primary outcomes:
measure: Improvement in Muscle energetics as measured by MR-spectroscopy
timeFrame: 24 weeks
Secondary outcomes:
measure: Short Performance Battery test
timeFrame: 24 weeks
measure: 6-Minute Walk Test
timeFrame: 24 weeks
measure: Change in Flow Mediated Dilatation
timeFrame: 24 weeks
measure: Markers of oxidative stress (F2-Isoprostanes)
timeFrame: 24 weeks
measure: Quality of Life measured by EuroQOL EQ5D questionnaire
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: University of Dundee Medical School
state: Angus
Study officials:
affiliation: University of Dundee
name: Jacob George, MRCP MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Dundee
name: Allan Struthers, MD FRCP
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Marion McMurdo, MD FRCP
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Miles Witham, PhD FRCP
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Graeme Houston, FRCP FRCR
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Steve Gandy, PhD
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Peter Donnan, PhD FRSS
role: STUDY_DIRECTOR
affiliation: University of Dundee
name: Clare Clarke, PhD MCSP
role: PRINCIPAL_INVESTIGATOR
References: