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

Prior treatment

• 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

Other illness

• Diabetes Mellitus requiring insulin or insulin secretagogue
• Unstable angina or history of acute myocardial infarction (\<5 days of planned study procedures)
• Uncontrolled arrhythmia causing symptoms
• Thrombosis of lower extremities
• 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)

Lab values

• Hemoglobin \< 10 g/dL
• Platelets \< 50K
• 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)

Other

• Known sensitivity to NR
• Currently meeting public health exercise guidelines
• Use of NAD+ precursors (supra-physiologic) within 4 weeks
• Limitations in physical function preventing exercise testing/training
• Recurrent syncope
• Symptomatic severe aortic stenosis
• Pulmonary embolus \<3 months of study procedures
• Symptomatic moderate or severe persistent asthma based on Forced Expiratory Volume (FEV) from pre-HCT pulmonary function testing
• Room air desaturation at rest ≤85%
• Females: Pregnant or planning pregnancy
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• 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.
• Current weight precludes safe completion of study procedures

• 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
• 6-48 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