Recruiting

Phase 2

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

Sponsor:

Children's Hospital of Philadelphia

Code:

NCT05194397

Conditions

Lymphoblastic Leukemia

Cancer Survivors

Aplastic Anemia

Myelodysplastic Syndromes

Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 10 - 30

Healthy Volunteers: Not accepted

Interventions

Nicotinamide Riboside

Placebo

Exercise Intervention

Study Details

Brief summary:

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.

Conditions

Lymphoblastic Leukemia

Cancer Survivors

Aplastic Anemia

Myelodysplastic Syndromes

Myeloid Leukemia

Study ID

NCT05194397

Start date

Feb 23, 2023

Status verified date

Dec, 2025

Completion date

Jun 30, 2026

Anticipated

Primary completion date

Jun 30, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 10 - 30

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Males and females, ages 10-30 years at enrollment
2. Able to understand and speak English
3. Diagnosis of leukemia (myeloid, lymphoid), aplastic anemia, bone marrow failure syndrome, or myelodysplastic syndrome requiring allogeneic HCT
4. 6-48 months from allogeneic HCT
5. Females must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
6. Subject's informed consent or parental/guardian permission (informed consent) and if appropriate, child assent
7. Minimum weight of 24 kg

Exclusion Criteria:

1. Known sensitivity to NR
2. Concurrent use of any medications, including statins, likely to increase risk of NR toxicity
3. Active malignancy, investigational agent(s) within 4 wks, or supraphysiological glucocorticoids at the baseline visit
4. Currently meeting public health exercise guidelines
5. Use of NAD+ precursors (supra-physiologic) within 4 weeks
6. Hemoglobin < 10 g/dL
7. Platelets < 50K
8. Diabetes Mellitus requiring insulin or insulin secretagogue
9. HbA1C ≥ 8% or fasting glucose > 125 mg/dL; However if the participant is diabetic, both fasting glucose level and HbA1C must meet the criteria to be deemed eligible.
10. Kidney disease (eGFR < 60 ml/min/1.73 m2)
11. Liver disease Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) (ALT/AST > 3 x ULN)
12. Limitations in physical function preventing exercise testing/training
13. Unstable angina or history of acute myocardial infarction (<5 days of planned study procedures)
14. Recurrent syncope
15. Symptomatic severe aortic stenosis
16. Uncontrolled arrhythmia causing symptoms
17. Pulmonary embolus <3 months of study procedures
18. Thrombosis of lower extremities
19. Symptomatic moderate or severe persistent asthma based on Forced Expiratory Volume (FEV) from pre-HCT pulmonary function testing
20. Room air desaturation at rest ≤85%
21. Females: Pregnant or planning pregnancy
22. Non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (e.g. infection, renal failure, thyrotoxicosis, >moderate Graft versus host disease (GVHD) resulting in physical or functional impairment)
23. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
24. For MRI procedure: Contraindications to MRI. Individuals will be screened to ensure they can safely complete the MRI. \*participants who cannot complete the MRI will not be excluded from participation in the remainder of the study procedures if they meet those inclusion and exclusion criteria.
25. Current weight precludes safe completion of study procedures

Study Design

Enrollment

80 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Nicotinamide Riboside (NR)

Investigators will use Good Manufacturing Process (GMP)-grade 300 mg capsules of the dietary supplement nicotinamide riboside (ChromaDex, Irvine CA). Investigators dose based on body weight, and monitor for adverse effects (AEs).

For individuals with weight > 72 kg: 900 mg po qd x 16 wks.

For individuals with weight > 48 kg and ≤ 72 kg: 600 mg po qd x 16 wks.

For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 16 wks.

placebo comparator: Placebo

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). Doses of placebo will match the body weight schema for dosing of NR. Investigators dose based on body weight, and monitor for adverse effects (AEs).

For individuals with weight > 72 kg: 900 mg po qd x 16 wks.

For individuals with weight > 48 kg and ≤ 72 kg: 600 mg po qd x 16 wks.

For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 16 wks.

experimental: Exercise Intervention and NR

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.

experimental: Exercise Intervention and Placebo

Interventions

Nicotinamide Riboside

Investigators 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

The 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

The 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.

Primary outcome measure

Within participant changes in muscle strength (Isometric knee extension, Z-score) [ Time Frame: Baseline to 16 Weeks ]

Central Contacts and Locations

Central contacts

Katherine Cambareri, MPH

445-942-7801 cambarerik@chop.edu

Kristin Wade

267-398-5761 wadekl@chop.edu

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Lanie Lindenfeld, MA, CCRP

626-218-1150 llindenfeld@coh.org

Principal Investigator:

Saro H Armenian, DO, MPH

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Susan Lee

267-602-4603 leess@chop.edu

Kristin Wade

267-398-5761 wadekl@chop.edu

Principal Investigator:

Sogol Mostoufi-Moab, MD, MSCE

St. Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Sarah Terrell, MS

901-595-4466 sarah.terrell@stjude.org

Principal Investigator:

Kirsten K. Ness, PhD

More Information

Sponsor

Children's Hospital of Philadelphia

Last update posted

Dec 4, 2025

Last verified

Dec, 2025

Keywords

Sarcopenia
NAD+
Exercise Intervention
OXPHOS Capacity
VO2 Max
Adolescent young adults
Cancer Survivors
Hematopoietic Stem Cell Transplantation (HCT)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Children's Hospital of Philadelphia on 2025-12-04.