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Completed

NCT Number: NCT02792621

Increasing Mitochondrial Function on Skeletal Muscle Performance in Older Men

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, by measuring how the muscles work and respond to exercise before and after taking the supplement. This will give us the basic information investigators would need to see if this is a useful idea.

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Key information

Age range

65 year–75 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

NIHR Exeter Clinical Research Facility

Exeter, Devon, EX2 5DW, United Kingdom

About this study

A defining feature of ageing is loss of muscle mass ('sarcopenia') and associated functional weakness ('dynapenia'). A common characteristic of dynapenia is lowered mitochondrial content and metabolic function, causing reduced aerobic capacity, increased sensations of effort and impaired lipid oxidation (with resultant glucose intolerance). Exercise training improves mitochondrial and muscle function in ageing populations, however such adaptations remain below that of young counterparts, suggesting alternative approaches are required. Pre-clinical studies show that dietary supplementation with precursors of nicotinamide adenine dinucleotide (NAD+) restore mitochondrial biogenesis and oxidative capacity in ageing rodents and diabetic humans. However, whether NAD+ precursors rejuvenate mitochondrial capacity and, ultimately, muscle function in older humans is unknown. This pilot project will therefore investigate the efficacy of NAD+ precursor supplementation for increasing muscle performance in normally active older men, combined with examination of the molecular and metabolic mechanisms regulating physiological responses.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Acipimox

Dietary Supplement

Oral supplement containing Acipimox 250mgs as the active ingredient in blinded label tablet form.

Placebo

Dietary Supplement

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.

Primary outcomes

  1. Change in mitochondrial function

    Time frame: Baseline, day 7, day 14

    Mitochondria will be extracted from muscle samples immediately post-biopsy (biopsies taken baseline, day 7 and day 14) and analysed for content and subsequently for oxidative respiratory function using the Seahorse technique, and maximal rates of Adenosine Triphosphate (ATP) production.

Secondary outcomes

  1. Chronic changes in habitual muscle protein synthetic rates

    Time frame: Baseline and then daily for 14 days

    baseline saliva samples then daily saliva samples 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.

Sponsors and collaborators

Lead sponsor

Royal Devon and Exeter NHS Foundation Trust

Other

Collaborators

  • University of Exeter

Registry information

Official study title

Assessing the Effects of Increased Mitochondrial Function on Skeletal Muscle Performance in Older Men; a Pilot Study

Acronym: Rejuvenate

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Jun 7, 2016
Registry last updated
Mar 10, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.