Exercise Training and NR Supplementation Trial to Improve Fitness in AYA HCT Survivors

What Was Tested

The trial (phase 2) is built around NAD+ for anemia.

This will be a randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise on skeletal muscle quality and VO2max in AYA HCT survivors.

The primary outcome is the change in muscle strength (isometric knee extension) from baseline to 16 weeks.

Key secondary outcomes are the change in muscle strength (ankle plantarflexion) from baseline to 16 weeks, the change in grip strength from baseline to 16 weeks, the change in lower extremity muscle mass from baseline to 16 weeks, the change in muscle OXPHOS capacity from baseline to 16 weeks, and the change in aerobic capacity (VO2 max) from baseline to 16 weeks.

It had four arms (groups): Nicotinamide Riboside (NR) (experimental), Placebo (placebo comparator), Exercise Intervention and NR (experimental) and Exercise Intervention and Placebo (experimental).

The exercise program consists of at-home training sessions including: aerobic and strengthening components designed to progress persons gradually to 150-300 minutes of the equivalent of moderate aerobic activity, and twice weekly strength training exercises. Participants in this arm will receive both the Exercise Intervention and the NR.

The registry classes the interventions as dietary supplement and other.

More on the Plan

Adolescents and young adults (AYAs) who undergo hematopoietic cell transplantation (HCT) are at an especially high risk of developing sarcopenia (loss of skeletal muscle mass), which occurs earlier than would be expected from advancing age alone.

This is important as not only it doubles their risk for non-relapse mortality, but it also leads to premature cardiovascular disease.

The investigators propose a mechanistic randomized controlled trial of home-based remotely supervised exercise (aerobic and resistance) training and supplementation with nicotinamide riboside, a precursor of NAD+, a metabolite that is critical for muscle metabolism, in AYA survivors of HCT.

Who Took Part

80 planned participants were the target.

It was open to people of any sex aged from 10 years up to 30 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Males and females, ages 10-30 years at enrollment. Able to understand and speak English. Diagnosis of leukemia (myeloid, lymphoid), aplastic anemia, bone marrow failure syndrome, or myelodysplastic syndrome requiring allogeneic HCT. 6-48 months from allogeneic HCT. Subject's informed consent or parental/guardian permission (informed consent) and if appropriate, child assent.

The full record lists 7 inclusion and 25 exclusion criteria; among the exclusions: known sensitivity to nr; active malignancy, investigational agent(s) within 4 wks, or supraphysiological glucocorticoids at the baseline visit; use of nad+ precursors (supra-physiologic) within 4 weeks.

How the Study Was Run

Design: randomized, factorial and quadruple-blind.

The anemia participants were allocated by chance, so the NAD+ group and the comparison group should start out alike.

Neither the anemia participants nor the staff measuring them knew who was on NAD+, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2023-02-23 with completion listed for 2026-06-30.

It ran at 3 sites in United States (3).

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Within participant changes in muscle strength (Isometric knee extension, Z-score) (time frame: Baseline to 16 Weeks).

It also tracked 5 secondary outcomes, for example Within participant change in muscle strength (Ankle Plantarflexion), Within participant change in grip strength (Hand Grip Dynamometry), Within participant changes in muscle mass (lower leg lean muscle mass by DXA), Within participant changes in post-exercise oxidative phosphorylation capacity (OXPHOS) and Within participant change in aerobic capacity (VO2 max, Maximal Oxygen Uptake on Cardiopulmonary Exercise Testing).

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of NAD+ in 80 people with anemia.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the NAD+ compound page, Anemia research.