Exercise and NAD+ Supplementation for Young Cancer Survivors

Intensive Tailored Exercise Training With NAD+ Precursor Supplementation to Improve Muscle Mass and Fitness in Adolescent and Young Adult Hematopoietic Cell Transplant Survivors

This study is testing if combining exercise with a supplement called nicotinamide riboside can help young cancer survivors improve their muscle strength and fitness.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 10 Years to 30 Years
• Sex: All
• Sponsor: Children's Hospital of Philadelphia (other)
• Locations: 3 sites (Duarte, California and 2 other locations)
• Trial ID: NCT05194397 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled trial investigates the effects of nicotinamide riboside (NR) supplementation and exercise training on muscle quality and aerobic capacity in adolescents and young adults (AYAs) who are survivors of hematopoietic cell transplantation (HCT) for leukemia and related conditions. The study employs a 2x2 factorial design, focusing on changes in muscle strength, lower extremity muscle mass, and VO2 max over a 16-week period. Participants will engage in home-based, remotely supervised aerobic and resistance training, alongside NR supplementation, to address the high risk of sarcopenia and its associated health risks in this population.

Who should consider this trial

Good fit: Ideal candidates are adolescents and young adults aged 10-30 years who have undergone allogeneic HCT for leukemia or related conditions within the last 6-48 months.

Not a fit: Patients currently meeting public health exercise guidelines or with active malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve muscle strength and aerobic capacity in young cancer survivors, enhancing their overall health and quality of life.

How similar studies have performed: Other studies have shown promising results with exercise interventions in cancer survivors, but the combination of NR supplementation and exercise in this specific population is novel.

Eligibility criteria

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

Where this trial is running

Duarte, California and 2 other locations

• City of Hope Medical Center — Duarte, California, United States (RECRUITING)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (RECRUITING)

Study contacts

• Principal investigator: Sogol Mostoufi-Moab, MD, MSCE — Children's Hospital of Philadelphia
• Study coordinator: Katherine Cambareri, MPH

Conditions: Lymphoblastic Leukemia, Cancer Survivors, Aplastic Anemia, Myelodysplastic Syndromes, Myeloid Leukemia, Sarcopenia, NAD+, Exercise Intervention