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NCT05194397 | RECRUITING | Lymphoblastic Leukemia

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

Children's Hospital of Philadelphia

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.

Condition or disease

Lymphoblastic Leukemia

Cancer Survivors

Aplastic Anemia

Myelodysplastic Syndromes

Myeloid Leukemia

Intervention/treatment

Nicotinamide Riboside

Placebo

Exercise Intervention

Phase

PHASE2

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 80 participants
Masking : QUADRUPLE
Masking Description : 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.
Primary Purpose : TREATMENT
Official Title : Intensive Tailored Exercise Training With NAD+ Precursor Supplementation to Improve Muscle Mass and Fitness in Adolescent and Young Adult Hematopoietic Cell Transplant Survivors
Actual Study Start Date : 2023-02-23
Estimated Primary Completion Date : 2026-06-30
Estimated Study Completion Date : 2026-06-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 10 Years to 30 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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
Exercise Training and NR Supplementation Trial to Improve Fitness in AYA HCT Survivors

Location Details

NCT05194397

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How to Participate

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Locations

RECRUITING

United States, California

City of Hope Medical Center

Duarte, California, United States, 91010

RECRUITING

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

RECRUITING

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105