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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Nicotinamide Riboside (NR) supplementation and exercise might enhance muscle strength and fitness in young adults who have survived cancer and undergone a stem cell transplant. Researchers aim to determine if these treatments can improve muscle quality and overall fitness levels. Participants will receive either the NR supplement, a placebo, or a combination of exercise with one of these. Individuals who had a bone marrow transplant 6 to 48 months ago for conditions like leukemia or anemia and struggle with regular exercise might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotinamide riboside (NR) is safe for people. Studies have found it to be well-tolerated, even at doses up to 1 gram per day over extended periods. One study found no significant differences in side effects between those taking NR and those taking a placebo, indicating that NR did not cause more issues than the placebo.

Exercise is also safe for cancer survivors. Research suggests that exercise programs, including those done at home, are generally safe and typically cause only minor side effects. Exercise often helps by improving muscle strength and overall health.

Both NR and exercise appear to be safe options based on current research. For those considering joining a trial involving these treatments, this information may be reassuring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Nicotinamide Riboside (NR) supplementation with exercise to potentially enhance recovery and overall well-being in cancer survivors. Unlike typical treatments for cancer recovery that focus mostly on rehabilitation through exercise alone, NR is a unique dietary supplement that may boost cellular energy and repair by increasing NAD+ levels, a critical molecule in the body’s metabolism. Combining NR with an exercise regimen could offer a dual approach: enhancing physical fitness while possibly accelerating cellular recovery. This innovative strategy aims to improve the quality of life for cancer survivors more effectively than current standard treatments.

What evidence suggests that this trial's treatments could be effective for cancer survivors?

Research has shown that nicotinamide riboside (NR), a type of vitamin B3, can improve muscle health. Studies have found that it increases levels of NAD+, a molecule important for energy, in the blood. This increase might lead to stronger muscles and better endurance. In this trial, some participants will receive NR alone, while others will receive NR combined with an exercise intervention.

Exercise has also been proven to benefit cancer survivors. Reviews indicate it reduces treatment side effects like tiredness and pain and improves quality of life. In this trial, some participants will receive an exercise intervention combined with a placebo. Together, NR and exercise could boost muscle strength and aerobic capacity, helping survivors regain physical fitness. ^{6 7 8 9 10}

Who Is on the Research Team?

Sogol Mostoufi-Moab, MD, MSCE

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

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

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

I am between 10 and 30 years old.

I weigh at least 24 kg.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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