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

NCT05194397 | Recruiting Phase 2 DMC

• 2 other identifiers: 20-0173201R01CA254955-01A1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 16 Weeks

Secondary Outcomes (5)

• Within participant change in muscle strength (Ankle Plantarflexion)

  Baseline to 16 Weeks

• Within participant change in grip strength (Hand Grip Dynamometry)

  Baseline to 16 Weeks

• Within participant changes in muscle mass (lower leg lean muscle mass by DXA)

  Baseline to 16 Weeks

• Within participant changes in post-exercise oxidative phosphorylation capacity (OXPHOS).

  Baseline to 16 Weeks

• Within participant change in aerobic capacity (VO2 max, Maximal Oxygen Uptake on Cardiopulmonary Exercise Testing).

  Baseline to 16 Weeks

Study Arms (4)

Nicotinamide Riboside (NR)

EXPERIMENTAL

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.

Dietary Supplement: Nicotinamide Riboside

Placebo

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Exercise Intervention and NR

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.

Dietary Supplement: Nicotinamide Riboside; Other: Exercise Intervention

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 Placebo

Dietary Supplement: Placebo; Other: Exercise Intervention

Interventions

Nicotinamide Riboside 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 and NR; Nicotinamide Riboside (NR)

Placebo 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 Placebo; Placebo

Exercise Intervention 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 NR; Exercise Intervention and Placebo

Eligibility Criteria

• Age: 10 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• months from allogeneic HCT
• 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.
• Subject's informed consent or parental/guardian permission (informed consent) and if appropriate, child assent
• Minimum weight of 24 kg

You may not qualify if:

• 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
• Use of NAD+ precursors (supra-physiologic) within 4 weeks
• Hemoglobin \< 10 g/dL
• Platelets \< 50K
• Diabetes Mellitus requiring insulin or insulin secretagogue
• 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.
• Kidney disease (eGFR \< 60 ml/min/1.73 m2)
• Liver disease Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) (ALT/AST \> 3 x ULN)
• Limitations in physical function preventing exercise testing/training
• Unstable angina or history of acute myocardial infarction (\<5 days of planned study procedures)
• Recurrent syncope
• Symptomatic severe aortic stenosis

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• University of Pennsylvania: collaborator
• Children's Hospital of Philadelphia: lead
• National Institutes of Health (NIH): collaborator
• City of Hope Medical Center: collaborator
• St. Jude Children's Research Hospital: collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 35854224 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Aplastic; Myelodysplastic Syndromes; Leukemia, Myeloid; Sarcopenia

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia; Bone Marrow Failure Disorders; Bone Marrow Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Sogol Mostoufi-Moab, MD, MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Cambareri, MPH

CONTACT

445-942-7801; cambarerik@chop.edu

Kristin Wade

CONTACT

267-398-5761; wadekl@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants and the investigator team will be blinded as to the group assignment: NR vs Placebo. All collected data (e.g., questionnaires) will be coded, so initial analysis will be conducted without knowledge of the participant's group status. While the assignment of participants to the exercise groups will not be blinded to the participant or majority of the study team, a designated blinded technician will perform the follow-up Cardio Pulmonary Exercise Testing. Follow-Up Cardio Pulmonary Exercise Testing will be performed by a dedicated blinded study team member, an exercise technician, who will not know if the participant was assigned to an arm including the exercise intervention.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise.

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: January 18, 2022
• Study Start: February 23, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: The investigator will make data available after the completion of the trial and posting of results on ClinicalTrials.gov and in conjunction with NIH policies.
• Access Criteria: Access will be limited to only using the data for research purposes that do not identify an individual participant and ensuring the data is securely maintained.

Locations

US (3)