RecruitingPhase 2NCT05194397

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

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

Sponsor

Children's Hospital of Philadelphia

Enrollment

80 participants

Start Date

Feb 23, 2023

Study Type

INTERVENTIONAL

Conditions

Cancer Survivors Myelodysplastic Syndromes Aplastic Anemia Lymphoblastic Leukemia Myeloid Leukemia

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.

Eligibility

Min Age: 10 YearsMax Age: 30 Years

Inclusion Criteria7

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

Exclusion Criteria24

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
Uncontrolled arrhythmia causing symptoms
Pulmonary embolus \<3 months of study procedures
Thrombosis of lower extremities
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
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)
Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Current weight precludes safe completion of study procedures

Interventions

DIETARY_SUPPLEMENTNicotinamide 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.

DIETARY_SUPPLEMENTPlacebo

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)

OTHERExercise 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.