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

NCT ID: NCT05194397

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-23
• Study Completion Date: 2026-06-30

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.

Detailed Description

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. The findings will lay the critical groundwork for future trials to prevent or mitigate the myriad downstream adverse effects of low muscle mass in AYA HCT survivors.

Conditions

Lymphoblastic Leukemia; Cancer Survivors; Aplastic Anemia; Myelodysplastic Syndromes; Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Nicotinamide Riboside

Intervention Type: DIETARY_SUPPLEMENT

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

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 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.

Group Type: EXPERIMENTAL

Nicotinamide Riboside

Intervention Type: DIETARY_SUPPLEMENT

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.

Exercise Intervention

Intervention Type: OTHER

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.

Exercise Intervention and Placebo

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 Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DIETARY_SUPPLEMENT

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

Intervention Type: OTHER

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.

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.

Intervention Type: DIETARY_SUPPLEMENT

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)

Intervention Type: DIETARY_SUPPLEMENT

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.

Intervention Type: OTHER

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.

25. Current weight precludes safe completion of study procedures

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sogol Mostoufi-Moab, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Katherine Cambareri, MPH

Role: CONTACT

cambarerik@chop.edu

445-942-7801

Kristin Wade

Role: CONTACT

wadekl@chop.edu

267-398-5761

Facility Contacts

Lanie Lindenfeld, MA, CCRP

Role: primary

llindenfeld@coh.org

626-218-1150

Susan Lee

Role: primary

leess@chop.edu

267-602-4603

Kristin Wade

Role: backup

wadekl@chop.edu

267-398-5761

Sarah Terrell, MS

Role: primary

sarah.terrell@stjude.org

901-595-4466

References

Song M, Armenian SH, Bhandari R, Lee K, Ness K, Putt M, Lindenfeld L, Manoukian S, Wade K, Dedio A, Guzman T, Hampton I, Lin K, Baur J, McCormack S, Mostoufi-Moab S. Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial 1. BMC Cancer. 2022 Jul 19;22(1):795. doi: 10.1186/s12885-022-09845-1.

Reference Type: DERIVED

PMID: 35854224 (View on PubMed)

Other Identifiers

1R01CA254955-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-017320

Identifier Type: -

Identifier Source: org_study_id