Intensive Tailored Exercise Training With NAD+ Precursor Supplementation to Improve Muscle Mass and Fitness in Adolescent and Young Adult Hematopoietic Cell Transplant Survivors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Within participant changes in muscle strength (Isometric knee extension, Z-score)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 10 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •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
研究组 & 干预措施
Placebo
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.
干预措施: Placebo (Dietary Supplement)
Exercise Intervention and 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 NR.
干预措施: Exercise Intervention (Other)
Exercise Intervention and Placebo
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
干预措施: Placebo (Dietary Supplement)
Exercise Intervention and Placebo
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
干预措施: Exercise Intervention (Other)
Exercise Intervention and 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 NR.
干预措施: Nicotinamide Riboside (Dietary Supplement)
Nicotinamide Riboside (NR)
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.
干预措施: Nicotinamide Riboside (Dietary Supplement)
结局指标
主要结局
Within participant changes in muscle strength (Isometric knee extension, Z-score)
时间窗: Baseline to 16 Weeks
Muscle Strength will be assessed by completion of isometric contractions using a Biodex dynamometer.
次要结局
- 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)