Assessing the Effects of Increased Mitochondrial Function Exercise Training on Muscle Performance

Study Overview
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Brief Summary
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As people grow older skeletal muscle gradually becomes smaller and weaker, causing reduced mobility and quality of life. To understand and reverse this negative process investigators need to find new ways of improving the ability of muscle to perform physical activity. There is some evidence that supplements may improve how the mitochondria work, and investigators want to explore this idea in more detail. This is possible by measuring how the muscles work and respond to exercise before and after taking the supplement alongside an aerobic (i.e. cycling) and resistance (i.e. weight lifting) exercise programme. This will give us the basic information investigators would need to see if this is a useful idea.

Official Title
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Assessing the Effects of Increased Mitochondrial Function and Chronic Aerobic or Resistance Exercise Training on Skeletal Muscle Performance in Older Men; a Pilot Study

Conditions
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Impaired Mitochondrial Function, Muscle Performance

Intervention / Treatment
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* Dietary Supplement: Acipimox
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age between 65-75 years Body mass index between 19-29 No active cardiovascular or metabolic disease No active respiratory disease No current musculoskeletal injuries A sedentary lifestyle (i.e. does not engage in strenuous, planned physical activity) The ability to give informed consent Exclusion Criteria: Currently taking a statin drug or NSAIDs Have a current peptic ulcer Have any renal impairment Have a known hypersensitivity to Acipimox Suffer from vertigo Smoker

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acipimox plus exercise training<br>The active supplement will contain the prescription drug Acipimox (250 mgs) , a nicotinic acid precursor traditionally used to lower blood lipid levels. The supplement will be administered 3 times per day, for 6 weeks. | Dietary Supplement: Acipimox<br>* Acipimox plus exercise training: Oral supplement containing Acipimox 250mgs as the active ingredient in blinded label tablet form.<br>|
| Placebo Comparator: Placebo plus exercise training<br>The placebo supplement will contain only cellulose microcrystalline. This is an inert substance widely used in many pill and tablet formulations. It is an insoluble fibre and is not absorbed into the blood stream therefore is unlikely to cause toxicity when taken orally. | Dietary Supplement: Placebo<br>* Alternate unilateral resistance and aerobic exercise training will also be performed 5 times per week for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mitochondrial function | Mitochondria will be extracted from muscle samples immediately post-biopsy (biopsies taken baseline, week 3 and week 6) and analysed for content and subsequently for oxidative respiratory function using the Oroboros technique, and maximal rates of Adenosine Triphosphate (ATP) production. | Baseline, 3 weeks, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic changes in habitual muscle protein synthetic rates | Baseline saliva samples then frequent saliva samples over 6 weeks following oral ingestion of the stable isotope deuterium oxide (D2O, or 'heavy water') will be analysed by gas-chromatography-pyrolysis-isotope ratio mass-spectrometry. analysis. Muscle samples collected at baseline, 3 weeks, 6 weeks will also be analysed by gas-chromatography-pyrolysis-isotope ratio mass-spectrometry | Baseline, 3 weeks and 6 weeks |