NR Supplementation + Exercise for Cancer Survivors

(IAMFIT Trial)

Recruiting at 2 trial locations

Overseen By Katherine Cambareri, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: Statins, Glucocorticoids, NAD+ precursors

Disqualifiers: Diabetes, Kidney disease, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you do not take any medications, including statins, that might increase the risk of NR toxicity. If you are on such medications, you may need to stop them to participate.

What data supports the effectiveness of this treatment for cancer survivors?

Research shows that exercise programs can improve physical functioning and quality of life for cancer survivors. Physical activity is recommended as part of care for all cancer survivors, with evidence supporting its benefits before, during, and after treatment. ^{1 2 3 4 5}

Is exercise safe for cancer survivors?

Research shows that exercise is generally safe for cancer survivors and can help maintain weight and bone mass, improve fatigue, and enhance quality of life. Exercise programs are recommended as they are practicable and beneficial during and after cancer treatment. ^{6 7 8 9 10}

How does the treatment of NR supplementation and exercise differ for cancer survivors?

This treatment is unique because it combines nicotinamide riboside (a form of vitamin B3) with both aerobic and resistance exercise, aiming to improve energy balance and physical function in cancer survivors. Unlike standard treatments, this approach focuses on enhancing overall health and quality of life through physical activity and nutritional supplementation. ^{1 9 11 12 13}

Research Team

Sogol Mostoufi-Moab, MD, MSCE

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for AYA HCT survivors aged 10-30 who speak English and are 6-48 months post-transplant. They must weigh at least 24 kg, not be pregnant, use contraception if applicable, and have parental consent if under age. Excluded are those with NR sensitivity, certain health conditions like severe diabetes or liver disease, recent heart issues or blood clots, asthma affecting lung function tests pre-HCT, or currently meeting exercise guidelines.

Inclusion Criteria

Able to understand and speak English

Parental/guardian permission (informed consent) and if appropriate, child assent

I am between 10 and 30 years old.

Exclusion Criteria

Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

I have severe symptoms from a narrowed heart valve.

I am pregnant or planning to become pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nicotinamide Riboside (NR) or placebo, and engage in a home-based exercise program for 16 weeks

16 weeks

Remote supervision

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exercise Intervention
• Nicotinamide Riboside
• Placebo

Trial Overview The study examines the impact of Nicotinamide Riboside (NR) supplementation and an exercise program on muscle strength and aerobic capacity in young cancer survivors. Participants will randomly receive either NR or a placebo while undergoing an exercise regimen to see how these interventions affect their physical fitness over a period of 16 weeks.

Participant Groups

Group I: Nicotinamide Riboside (NR) Experimental Treatment 1 Intervention

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.

Group II: Exercise Intervention and Placebo Experimental Treatment 2 Interventions

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

Group III: Exercise Intervention and NR Experimental Treatment 2 Interventions

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.

Group IV: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

St. Jude Children's Research Hospital

Collaborator

Trials

451

Recruited

5,326,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Findings from Research

Physical activity has been shown to significantly improve both patient-reported outcomes and physiological health in cancer survivors during and after treatment, highlighting its importance in recovery.

The review discusses ongoing phase III trials that are investigating the impact of physical activity on clinical disease endpoints, suggesting a strong focus on integrating exercise into cancer care to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Putting Exercise Into Oncology Practice: State-of-the-Science, Innovation, and Future Directions. Brown, JC., Ligibel, JA.[2023]

Exercise programs significantly improve various health indicators in adult cancer patients after completing their main treatment, particularly in areas like muscle strength, fatigue, depression, and quality of life, based on a review of 34 studies.

Patients with breast cancer showed notable benefits from aerobic exercise, with improvements in physical functions such as a 29-meter increase in 6-minute walk distance, highlighting the efficacy of exercise in enhancing recovery and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise programs for patients with cancer improve physical functioning and quality of life. McClellan, R.[2013]

Exercise and physical activity are crucial for cancer survivors, as they help combat reduced physical function and improve overall health during and after treatment.

Combining aerobic and resistance training is especially beneficial for patients experiencing cachexia, and emerging evidence suggests that nutritional support alongside exercise can enhance these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training in cancer patients. Maddocks, M.[2021]

A systematic review of 26 trials involving cancer survivors showed that various forms of exercise (aerobic, resistance, and mixed-mode) significantly improve bone mineral density (BMD) outcomes, particularly in the whole body, hip, and femoral neck.

The study supports the recommendation of exercise as an effective intervention for preventing bone loss in cancer survivors, with most trials being supervised and lasting from 12 weeks to 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exercise for improving bone health in cancer survivors - A systematic review and meta-analysis. Singh, B., Toohey, K.[2021]

An 8-week exercise-based rehabilitation program for cancer survivors was found to be safe and feasible, with 61% of eligible participants starting the program and high satisfaction reported among attendees.

Participants showed clinically significant improvements in physical function and quality of life, with an average increase of 73 meters in walking distance and an 8-unit increase in quality of life scores, indicating the program's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bridging the gap: a pre-post feasibility study of embedding exercise therapy into a co-located cancer unit. Dennett, AM., Zappa, B., Wong, R., et al.[2021]

A pilot study involving 24 adolescent and young adult cancer survivors showed that an 8-week program of exercise and nutrition education significantly improved fatigue levels and quality of life, as well as health-related fitness measures like cardiovascular endurance and muscular strength.

Participants reported enhanced nutrition knowledge and confidence in making healthy choices, indicating that exercise programs with social support can be beneficial as an additional therapy for cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise with Nutrition Education to Improve Quality of Life of Adolescent and Young Adult Cancer Survivors: A Pilot Study. DeNysschen, CA., Panek-Shirley, LM., Zimmerman, B.[2021]

Exercise is an effective rehabilitative intervention for cancer survivors, as it helps maintain body weight and bone mass, particularly in a high-risk population like breast cancer survivors, based on findings from 25 randomized controlled trials.

While most trials showed no significant weight change, some indicated reductions in fat mass and increases in lean mass, highlighting the need for further research to optimize exercise interventions for improving quality of life in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and cancer. Knobf, MT., Winters-Stone, K.[2014]

The Flinders Living Well Self-Management Program™ (FLW Program) is a feasible and acceptable intervention for Australian cancer survivors, showing promise in maintaining muscle mass and improving exercise capacity during and after treatment.

Participants in the program experienced small but positive changes in body composition and significant improvements in global health status, particularly in those who were post-treatment, suggesting that early implementation during chemotherapy could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Self-Management-based Nutrition and Physical Activity Intervention in Cancer Survivors. Miller, M., Zrim, S., Lawn, S., et al.[2018]

Resistance exercise (RE) has been shown to significantly improve muscular strength (large effect size of 0.86) and physical function (moderate effect size of 0.66) in cancer patients and survivors, based on a systematic review of 15 studies involving 1,077 participants.

RE also leads to small but meaningful improvements in body composition and quality of life outcomes, suggesting it is an effective supportive care intervention alongside traditional aerobic exercise during and after cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance exercise interventions during and following cancer treatment: a systematic review. Focht, BC., Clinton, SK., Devor, ST., et al.[2022]

Physical activity and exercise therapy are beneficial for cancer patients during treatment and recovery, helping to manage side effects and improve overall outcomes.

Integrating nutrition therapy with physical activity into cancer treatment plans can enhance patient care and should be considered for both cancer patients and the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supportive Care in Oncology-From Physical Activity to Nutrition. Schmidt, T., Süß, P., Schulte, DM., et al.[2022]

Interventions promoting exercise and healthy body weight are increasingly recognized as important for improving the long-term health of cancer survivors, addressing issues like obesity and physical inactivity.

The review highlights differences in research and clinical priorities between Europe and North America regarding energy balance interventions, suggesting a need for international collaboration to enhance care and outcomes for post-treatment cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions to promote energy balance and cancer survivorship: priorities for research and care. Alfano, CM., Molfino, A., Muscaritoli, M.[2023]

Adding behavioral counseling to a 4-week supervised physical activity program for kidney cancer survivors showed feasibility and a potential increase in physical activity levels, although the increase was not statistically significant.

Participants receiving behavioral counseling improved their 6-minute walk distance significantly more than those receiving standard exercise counseling, suggesting that behavioral strategies may enhance fitness outcomes in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and preliminary efficacy of adding behavioral counseling to supervised physical activity in kidney cancer survivors: a randomized controlled trial. Trinh, L., Plotnikoff, RC., Rhodes, RE., et al.[2014]

In a study involving 14 cancer patients undergoing treatment, a 4-week NMES (neuromuscular electrical stimulation) exercise intervention significantly improved functional muscle strength and exercise capacity, with participants able to perform more sit-to-stand repetitions and walk further in 6 minutes.

No adverse events were reported during the intervention, suggesting that NMES exercise is a safe and effective option for enhancing physical function in cancer patients with moderate to poor functional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional, physiological and subjective responses to concurrent neuromuscular electrical stimulation (NMES) exercise in adult cancer survivors: a controlled prospective study. O'Connor, D., Lennon, O., Fernandez, MM., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Putting Exercise Into Oncology Practice: State-of-the-Science, Innovation, and Future Directions. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Exercise programs for patients with cancer improve physical functioning and quality of life. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training in cancer patients. [2021]

4. Australia pubmed.ncbi.nlm.nih.gov

The effect of exercise for improving bone health in cancer survivors - A systematic review and meta-analysis. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Bridging the gap: a pre-post feasibility study of embedding exercise therapy into a co-located cancer unit. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Exercise with Nutrition Education to Improve Quality of Life of Adolescent and Young Adult Cancer Survivors: A Pilot Study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Exercise and cancer. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

A Pilot Study of Self-Management-based Nutrition and Physical Activity Intervention in Cancer Survivors. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Resistance exercise interventions during and following cancer treatment: a systematic review. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Supportive Care in Oncology-From Physical Activity to Nutrition. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Interventions to promote energy balance and cancer survivorship: priorities for research and care. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Feasibility and preliminary efficacy of adding behavioral counseling to supervised physical activity in kidney cancer survivors: a randomized controlled trial. [2014]

13. England pubmed.ncbi.nlm.nih.gov

Functional, physiological and subjective responses to concurrent neuromuscular electrical stimulation (NMES) exercise in adult cancer survivors: a controlled prospective study. [2021]