Effect of Allopurinol Administration on the Prevention of Muscle Mass Loss in Subject Immobilized.

Generating critical levels of power is a prerequisite for performing simple daily activities, such as rising from a chair or climbing stairs. For a young healthy person these activities can be performed easily, however after a prolonged period of forced inactivity (such as during the recovery from a sports injury, prolonged bed rest or spaceflight) a loss of muscle mass occurs. It has been suggested that this loss may be triggered by oxidative stress. An enzyme involved in the production of free radicals in various experimental models, including immobilization, is xanthine oxidase (XO). Although allopurinol is an inhibitor of XO widely used in clinical practice, its effect on the maintenance of muscle mass after an immobilization protocol is unknown. Thus, the major aim of this clinical trial is to determine the effect of allopurinol administration on the prevention of muscle mass loss in immobilized subjects.

This is a prospective, randomized study in which fifty young male subjects (aged between 25 and 40 years) diagnosed with grade II ankle sprain will be recruited. After immobilization the patients will be assigned randomly to one of two experimental groups, one treated with allopurinol (n=25) and the other with placebo (n=25). The dosage of allopurinol will be the same as recommended for gout patients, i.e. 300 mg/day orally, during all the immobilization period, which will last fifteen days. This medication will be delivered to the patients when they agree to participate in the clinical trial. They will be immobilized by posterior knee splint, preventing use of that leg.

We will determine muscle mass loss by performing two magnetic resonances of both legs before and after the immobilization period. We will also take two blood samples (before and after immobilization) to measure oxidative stress parameters (malondialdehyde, protein carbonyls, and XO activity), inflammatory parameters (IL-6, C-reactive protein and 1-antichymotrypsin), as well as vitamin D levels.

Study Overview

• Status: Completed
• Conditions: Patients With Grade II Ankle Sprain
• Intervention / Treatment: Drug: Placebo; Drug: Allopurinol

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46010
    • University of Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients with grade II sprain.
• Boys
• Age 20-40 years.
• Patient without regular medication.
• All patients must provide written informed consent specific to this study complete.

Exclusion Criteria:

• Liver and gastrointestinal disease.
• Untreated hypothyroidism.
• Alcohol and / or drug addiction.
• Vitamin supplements.
• Eating Disorders.
• Drugs that decrease the concentration of lipids.
• Antihypertensive drugs.
• Athletes who exercise intensely.
• Mental disorders, depression or anxiety intensive. These conditions make the patient unable to understand the nature or the scope and possible consequences of the study.
• Patients presenting an infectious process and / or inflammatory before collecting the sample.
• Patients may not follow the protocol because of its lack of cooperation, to their inability to return to subsequent visits and there is little chance of completing the study procedures.
• Hypersensitivity to allopurinol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allopurinol; One tablet of allopurinol is administrated orally at a dose of 300 mg/24 hours, during the time that the patient remains immobilized for 15 days.	Drug: Allopurinol; Other Names: Zyloric; 1H-pirazolo (3,4-d)pirimidina-4-ol
Placebo Comparator: Placebo; One tablet/24 hours of placebo orally, during the time that the patient remains immobilized for 15 days.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle mass loss	Checks the loss of muscle mass percentage with Magnetic Resonance before and after treatment.	Day 0 and day 15
The role of xanthine oxidase in the loss of muscle mass	Measure xanthine oxidase activity in plasma	Day 0 and day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
size of the leg muscles in a group of immobilized subjects.	Checks the loss of muscle mass size with Magnetic Resonance before and after treatment.	Day 0 and day 15
oxidative stress parameters	Glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA) and oxidized proteins, after a period of immobilization of 15 days duration.	Day 0 and day 15

Collaborators and Investigators

• Sponsor: Instituto de Investigacion Sanitaria La Fe
• Investigators: Study Director: JOSÉ VIÑA, MD PhD (HON), University of Valencia

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: November 12, 2013
• First Submitted That Met QC Criteria: November 12, 2013
• First Posted (Estimate): November 19, 2013

Study Record Updates

• Last Update Posted (Estimate): September 8, 2016
• Last Update Submitted That Met QC Criteria: September 7, 2016
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Magnetic resonance; Xanthine oxidase
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Ankle Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: ALMU_2011; 2011-003541-17 (EudraCT Number)