Clinical trial NCT04691986: Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans
Official title: Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sarcopenia
Nicotinamide Adenine Dinucleotide Concentration
Muscle Quality and NAD+ Content
Keywords: muscle
strength
endurance
gait speed
grip strength
frailty
muscle fibers
mitochondria
inflammation
resilience
aging
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University at Buffalo
First posted: 2020-12-31
Enrollment: 144
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will be conducted as a double-blind randomized controlled trial. Participants will be randomly assorted to receive either the nicotinamide riboside supplementation or a placebo pill.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Frailty is an age-associated clinical condition of poor physiological reserve that increases risks for falls, hospitalization and mortality. Nicotinamide adenine dinucleotide (NAD) is a critical co-factor needed for many cellular processes. The natural levels of NAD decline aging and this has been linked to physical performance decline in animals. Human trials have demonstrated that nicotinamide riboside (NR), a form of vitamin B3, is safe and effectively increases NAD+ levels. In animal studies, NR improves treadmill performance and muscle quality. Here the investigators propose a double-blind randomized control trial to assess the benefits of NR supplementation on human muscle function and physiology. The investigators anticipate the research findings will support the use of this nutritional supplement to improve the health of Veterans during aging.

Detailed description: Frailty is increasingly seen within the aging population and is driven largely by musculoskeletal declines. Nearly 9 million Veterans are now 65 years of age or older with impairments in functional capacity, reduction in quality of life, and an increase in the use of health care services and associated costs. An estimated 45-50% of those over the age of 85 are frail, which could represent well over 1 million Veterans. Aging, which significantly contributes to frailty, is highly correlated with reduced levels of nicotinamide adenine dinucleotide (NAD+), an essential mediator in mitochondrial function. Restoration of cellular NAD+ levels is gaining support as a therapeutic strategy to maintain and even enhance functional capacity during aging. Nicotinamide riboside (NR) - an NAD+ precursor - enhances physical activity and mitochondrial health in mice. Furthermore, NR was recently shown to be safe in human clinical trials for boosting NAD+, yet the benefits for human physical performance and muscle physiology are unknown. Therefore, the goal of this project is to establish a double-blind randomized control trial to assess the impacts of NR on functional capacity, muscle function and structure, and mRNA signaling in healthy older adults. Towards this goal, this study will investigate healthy older individuals between the ages of 65 and 85 who will receive NR or a placebo for a period of 3 months. Participants will be tested for frailty, gait speed, and muscle strength at each time point. Additionally, muscle biopsies and serum will be collected to assess changes in muscle fiber histology, mitochondrial biomass and activity, and mRNA profiles. This project will provide greater insight into NR supplementation as a therapeutic strategy to stave off frailty and maintain resilience during aging.

Eligibility criteria: Inclusion Criteria:

* Ages 65-85
* Male or female
* Any race
* Ability to use an exercise bike
* Medically cleared for muscle biopsy

Exclusion Criteria:

* Severe Co-morbidity

  * examples include, but not limited to:
  * congestive heart failure class equal to or above III
  * chronic obstructive pulmonary disorder (COPD) gold stage IV
  * chronic kidney disease equal to or above stage
* A VA-SLUMS cognitive screen score of less than or equal to 20
* Body mass index greater than or equal to 40

Primary outcomes:
measure: Sub-maximal oxygen uptake test (VO2max)
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Muscle strength
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Gait speed
timeFrame: Change from baseline to endpoint at 12 weeks
Secondary outcomes:
measure: Frailty assessment
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Short Physical Performance Battery
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Quality of life assessment
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Cognitive screen
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Serum inflammatory biomarkers
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Body Composition (Lean and fat mass)
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Blood occlusion resilience
timeFrame: Change from baseline to endpoint at 12 weeks
measure: 6-minute walk and heart rate recovery
timeFrame: Change from baseline to endpoint at 12 weeks
measure: Balance resistance
timeFrame: Change from baseline to endpoint at 12 weeks
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Kansas City VA Medical Center, Kansas City, MO
state: Missouri
Study officials:
affiliation: Kansas City VA Medical Center, Kansas City, MO
name: Kenneth L Seldeen, PhD
role: PRINCIPAL_INVESTIGATOR
References: