Exercise Training and NR Supplementation Trial to Improve Fitness in AYA HCT Survivors (IAMFIT)
Acute Lymphoblastic Leukemia in Remission, Cancer Survivors, Aplastic Anemia
About this trial
This is an interventional other trial for Acute Lymphoblastic Leukemia in Remission focused on measuring Sarcopenia, NAD+, Exercise Intervention, OXPHOS Capacity, VO2 Max, Adolescent young adults, Cancer Survivors, Hematopoietic Stem Cell Transplantation (HCT)
Eligibility Criteria
Inclusion Criteria:
- Males and females, ages 10-30 years at enrollment
- Able to understand and speak English
- Diagnosis of acute leukemia (myeloid, lymphoid) requiring allogeneic HCT
- 6-24 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.
- Parental/guardian permission (informed consent) and if appropriate, child assent
- Minimum weight of 24 kg
Exclusion Criteria:
- 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 systemic glucocorticoids within 12 wks
- 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%
- Kidney disease (eGFR < 60 ml/min/1.73 m2)
- Liver disease Alanine aminotransferase/Aspartate aminotransferase(ALT/AST) > 3 x ULN
- Limitations in physical function preventing exercise testing/training
Contraindications to MRI. Including:
- ANY intra-luminal implant, filter, stent or valve replacement
- ANY type of life assist device, pump, or prosthetic
- ANY vascular clip or clamp
- ANY surgically placed clips or clamps or bands on visceral organs
- ANY intracranial implants of any type other than dental fillings
- ANY non-removable piercings, jewelry, or medicinal patch
- ANY personal history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic examination.
- ANY personal history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation.
- Inability to lie flat in the MRI scanner for 60-90 minutes
- 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.
Sites / Locations
- City of Hope Medical CenterRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Placebo Comparator
Experimental
Experimental
Nicotinamide Riboside (NR)
Placebo
Exercise Intervention and NR
Exercise Intervention and Placebo
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.
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.
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.
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