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.
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
Known sensitivity to NR
Concurrent use of any medications, including statins, likely to increase risk of NR toxicity
Active malignancy, investigational agent(s) within 4 wks, or supraphysiological glucocorticoids at the baseline visit
Currently meeting public health exercise guidelines
Factorial
Nicotinamide Riboside
Dietary supplementInvestigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside (ChromaDex, Irvine CA). NR is distributed by ChromaDex, Inc., Irvine, CA. NR is available as 300 mg capsules. The dietary supplement will be re-labeled by the Hospital of the University of Pennsylvania (HUP) Investigational Drug Service according to FDA regulations, including subject and physician name and NR or Placebo 300 mg capsules.
Placebo
Dietary supplementThe matched placebo will contain the same excipients without the active supplement and is generally recognized as safe. The placebo will be covered in an identical capsule (NR will be covered in the same capsule)
Exercise Intervention
Other interventionThe exercise program consists of at-home training sessions and will include aerobic and strengthening components designed to progress persons gradually to 150-300 minutes of the equivalent of moderate aerobic activity, and twice weekly strengthening over 16 weeks. For aerobic training, the eventual intensity and duration goal (adapted for each person as necessary) will be for persons to train at 70-80% of peak 2MSPT heart rate 20-45 minutes 3-5 days/week. For resistance exercises the goal will be a load/weight that results in fatigue after 3 sets of 10-12 repetitions on 8-10 exercises 2 days/week.
Within participant changes in muscle strength (Isometric knee extension, Z-score)
Muscle Strength will be assessed by completion of isometric contractions using a Biodex dynamometer.
Within participant change in muscle strength (Ankle Plantarflexion)
Muscle Strength will be assessed by completion of isometric contractions using a Biodex dynamometer.
Within participant change in grip strength (Hand Grip Dynamometry)
Grip Strength will be assessed using a hand grip dynamometry device.
Within participant changes in muscle mass (lower leg lean muscle mass by DXA)
Muscle mass will be assessed by completion of whole body DXA scanning.
Within participant changes in post-exercise oxidative phosphorylation capacity (OXPHOS).
OXPHOS capacity will be assessed by completion of non-invasive MRI scanning using creatine chemical exchange saturation transfer (CrCEST).
Click on the lead sponsor to view all of their trials.
Children's Hospital of Philadelphia
Lead sponsor
National Institutes of Health (NIH)
Collaborator
City of Hope Medical Center
Collaborator
St. Jude Children's Research Hospital
Collaborator
National Cancer Institute (NCI)
Collaborator
University of Pennsylvania
Collaborator
