Clinical trial NCT03754842: Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans
Official title: Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans - A Randomized, Placebo-controlled, Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Injury
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2018-11-27
Enrollment: 32
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Successful skeletal muscle regeneration depends on a functional pool of muscle stem cells, termed satellite cells (SC). SC are in a quiescent state throughout adulthood, but undergo multiple cycles of proliferation and self-renewal in response to muscle damage. During aging, there is a loss of SC quiescence, and SC more readily enter an ageing-state impairing their function.

Animal studies have revealed a common denominator for increasing SC function and activity, namely Sirtuin activation. Natural stimulators of Sirtuins includes Nicotinamide Riboside (NR) (a Nicotinamide adenine dinucleotide (NAD+) precursor) and the polyphenol Pterostilbene (PT). In this study, we aim to investigate if NR+PT supplementation will promote skeletal muscle regeneration after muscle damage in elderly humans by enhanced recruitment of SC.

Detailed description: 14 days after start of placebo or NR/PT (500/100 mg twice daily) supplementation a muscle damage will induced in the m. vastus lat. by electric stimulation combined with eccentric work in a dynamometer. Muscle biopsies will be collected at 2 hours, 2, 8 and 30 days post damage and placebo or NR/PT supplementation will continue for the whole study period (45 days).

Eligibility criteria: Inclusion Criteria:

* Written signed consent
* Age: 55-80
* BMI: 20-28 (kg/(m2))
* Non-smoker

Exclusion Criteria:

* Endocrine disease, neurological or muscle disease
* Other severe disease
* High daily activity level (\>30 min / day)

Primary outcomes:
measure: Presence of Satellite Cells
timeFrame: Change from baseline up to 45 days
Secondary outcomes:
measure: Activation of Satellite cells
timeFrame: Change from baseline up to 45 days
measure: Presence of macrophages
timeFrame: Change from baseline up to 45 days
measure: Presence of Fibro/Adipogenic Progenitors
timeFrame: Change from baseline up to 45 days
measure: Presence of damaged muscle fibers
timeFrame: Change from baseline up to 45 days
measure: Presence of muscle regenerative fibers
timeFrame: Change from baseline up to 45 days
measure: Presence of autophagy in relation to muscle damage
timeFrame: Change from baseline up to 45 days
measure: Lipid accumulation in skeletal muscle tissue and liver
timeFrame: Change from baseline to 8 days
measure: Blood glucose response in relation to muscle damage
timeFrame: Change from baseline to 8 days
measure: Body composition (lean body mass and fat body mass)
timeFrame: Change from baseline to 45 days
measure: Muscle strength
timeFrame: Change from baseline up to 45 days
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
Study officials:
References:
citation: Jensen JB, Dollerup OL, Moller AB, Billeskov TB, Dalbram E, Chubanava S, Damgaard MV, Dellinger RW, Trost K, Moritz T, Ringgaard S, Moller N, Treebak JT, Farup J, Jessen N. A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals. JCI Insight. 2022 Oct 10;7(19):e158314. doi: 10.1172/jci.insight.158314.