Increasing Mitochondrial Function on Skeletal Muscle Performance in Older Men

Impaired Mitochondrial Function, Muscle Performance Clinical Trial

— Rejuvenate  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792621
• Other study ID #: R&D no 1608287
• Status: Completed
• Phase: N/A
• Start date: November 8, 2016
• Est. completion date: December 15, 2019

Study information

• Verified date: April 2018
• Source: Royal Devon and Exeter NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 15, 2019
• Est. primary completion date: June 26, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 65 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Impaired Mitochondrial Function, Muscle Performance

Intervention

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

Locations

Country	Name	City	State
United Kingdom	NIHR Exeter Clinical Research Facility	Exeter	Devon

Sponsors (2)

Lead Sponsor	Collaborator
Royal Devon and Exeter NHS Foundation Trust	University of Exeter

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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