Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans

Sarcopenia Clinical Trial

— NR-VET  

Official title:

Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04691986
• Other study ID #: E3396-R
• Secondary ID: RX003396
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: October 2023
• Source: VA Office of Research and Development
• Contact: Kenneth L Seldeen, PhD
• Phone: (716) 888-4869
• Email: Kenneth.Seldeen[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Quality and NAD+ Content
• Nicotinamide Adenine Dinucleotide Concentration
• Sarcopenia

Intervention

Dietary Supplement:
• Nicotinamide Riboside
Nicotinamide Riboside is a form of vitamin B3 and is naturally occurring in humans.

Other:
• Placebo
Placebo pills contain micro cellulose powder.

Locations

Country	Name	City	State
United States	Kansas City VA Medical Center, Kansas City, MO	Kansas City	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	University at Buffalo

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal oxygen uptake test (VO2max)	Participants are asked to exercise on an upright exercise bike as the resistance increases over time. During the exercise, participants are asked to breath through a mask that is connected to a oxygen and carbon dioxide measuring device. The assessment last for approximately 5-10 minutes and provides data the pertain to an individuals lung capacity, breathing rate, and endurance.	Change from baseline to endpoint at 12 weeks
Primary	Muscle strength	Leg and arm strength will be measured using a small handheld dynamometer where the device is placed on the wrist or ankle as the participant is asked to extend or contract the limb with full force.	Change from baseline to endpoint at 12 weeks
Primary	Gait speed	Participants are asked to perform a timed walk of approximately 15 feet in length	Change from baseline to endpoint at 12 weeks
Secondary	Frailty assessment	Frailty is a syndrome marked by greater susceptibility to adverse outcomes like falls and disability. Frailty diagnosis in this study is conducted as having 3 or more of the following risk factors - unexpected weight loss in a 1 year time frame, weak grip strength measured by a hand dynamometer device, slow gait speed in a 15 foot walk test, low activity levels assessed with a survey question, and poor endurance also assessed by a survey question.	Change from baseline to endpoint at 12 weeks
Secondary	Short Physical Performance Battery	The Short physical performance battery (SPPB) is a battery of test often used in geriatric research to capture functional capacity in older adults. The test includes a balance and coordination assessment via asking participants to hold stances with different foot positions, a gait speed test of approximately 8 feet, and a chair rise timed test where a participant is asked to rise from a chair 5 times.	Change from baseline to endpoint at 12 weeks
Secondary	Quality of life assessment	Quality of life assessment is performed using the Quality of life, enjoyment, and satisfaction questionnaire - short form (Q-LES-Q-SF) survey instrument. The survey instrument scores from 0 to 70 with a greater score representing better quality of life.	Change from baseline to endpoint at 12 weeks
Secondary	Cognitive screen	Cognitive status will be assessed using the VA - St. Louis University Mental Survey (VA-SLUMS) involving memory tests, shape recognition, and story recall. The survey scores range from 0-30, with a higher score representing greater cognitive capability.	Change from baseline to endpoint at 12 weeks
Secondary	Serum inflammatory biomarkers	Chronic inflammation may be indicative of distress and lead to chronic diseases. The study will examine changes in inflammatory markers, C-reactive protein, interleukin-6, and interleukin-10.	Change from baseline to endpoint at 12 weeks
Secondary	Muscle analysis, including NAD+ content, mitochondrial health, and muscle fiber analyses, messageRNA	A muscle biopsy will be performed at baseline and endpoint. From this sample extracts will be created to assess changes in muscle NAD+ content (an expected response from NR supplementation). Additionally, mitochondria will be isolated and assessed for overall content and basal and maximal activity. Finally, the muscle sample will be assessed using histology to observe changes in fiber size and if there is a difference in the number of slow and fast twitch muscle fibers. Finally, changes in message RNA expression will be determined in order to understand how treatment affects cellular function.	Change from baseline to endpoint at 12 weeks
Secondary	Body Composition (Lean and fat mass)	Body composition will be measured using bioelectric impedance (BIA) - a technique where participants are asked to stand on the measurement device and hold on to two metal handles. A light - and non-detectable - current is then transmitted allowing for collection of body fat and lean mass in the subject. The assessment takes roughly 2-3 minutes.	Change from baseline to endpoint at 12 weeks