Increasing Mitochondrial Function on Skeletal Muscle Performance in Older Men (Rejuvenate)

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

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.

Study Overview

• Status: Completed
• Conditions: Impaired Mitochondrial Function, Muscle Performance
• Intervention / Treatment: Dietary supplement: Acipimox; Dietary supplement: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • NIHR Exeter Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active oral supplement; 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 a 14 day period.	Dietary supplement: Acipimox; Oral supplement containing Acipimox 250mgs as the active ingredient in blinded label tablet form.
Placebo Comparator: placebo 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.	Dietary supplement: placebo; 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.

What is the study measuring?

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, 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.	Baseline, day 7, day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic changes in habitual muscle protein synthetic rates	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.	Baseline and then daily for 14 days

Collaborators and Investigators

• Sponsor: Royal Devon and Exeter NHS Foundation Trust
• Collaborators: University of Exeter
• Investigators: Study Director: Timothy Etheridge, PhD, University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2016
• Primary Completion (Actual): June 26, 2018
• Study Completion (Actual): December 15, 2019

Study Registration Dates

• First Submitted: May 24, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimate): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Acipimox
• Other Study ID Numbers: R&D no 1608287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO