Exercise for Graft-versus-Host Disease

(RESTART Trial)

Recruiting at 1 trial location

Overseen By Christina M Dieli-Conwright, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Must be taking: Corticosteroids

Must not be taking: Investigational agents

Disqualifiers: Active infection, Diabetes, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 12 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a home-based exercise program can help people with Graft-Versus-Host Disease (GVHD), a condition that can occur after a stem cell transplant. Participants will either engage in aerobic and resistance exercises or follow a stretching routine. The researchers aim to determine if these exercises are practical and beneficial for those dealing with GVHD. Individuals who have recently started steroid treatment for GVHD and currently do less than 60 minutes of structured exercise each week might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to understanding how exercise can aid those with GVHD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs, chemotherapy, or radiation therapy.

What prior data suggests that this exercise intervention is safe for patients with GVHD?

Research has shown that exercise is generally safe for individuals who have received a stem cell transplant from a donor. Studies have found that physical activity can improve heart health, increase strength, and enhance quality of life. It can also help reduce fatigue in these patients. While exercise is usually well-tolerated, following a program that suits individual health needs is important. This trial will explore whether a specific combination of aerobic and strength exercises is suitable for those with Graft-versus-Host Disease (GVHD). ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using exercise to manage Graft-versus-Host Disease (GVHD) because it offers a non-pharmacological approach that differs from standard treatments like immunosuppressive drugs. Unlike medications that often come with significant side effects, exercise is a natural intervention that can improve overall health and quality of life. The study treatment involves a unique, home-based program delivered virtually, combining aerobic and resistance exercises, making it accessible and tailored to individual needs. This method not only aims to alleviate GVHD symptoms but also promotes long-term health benefits without the risks associated with drug therapies.

What evidence suggests that this trial's exercise interventions could be effective for Graft-versus-Host Disease?

Research shows that exercise, such as aerobic and resistance training, might help people with graft-versus-host disease (GVHD). Some studies suggest that exercise can improve mobility and quality of life for these patients. However, not all research has found clear benefits. For instance, one study did not find major improvements in fitness or fatigue from high-intensity exercise. In this trial, participants in the Exercise Group will engage in a home-based, virtually supervised aerobic and resistance exercise program. Meanwhile, the Attention Control Group will participate in a home-based stretching program. Researchers continue to study how exercise might benefit GVHD patients. While evidence is mixed, exercise is being considered as a potential way to aid recovery and improve overall health for these individuals. ^{1 2 3 4 5}

Who Is on the Research Team?

Christina M Dieli-Conwright, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had an allogeneic stem cell transplant at Dana-Farber Cancer Institute, are newly diagnosed with acute or chronic GVHD, and starting high-dose corticosteroids. They should do less than 60 minutes of structured exercise per week, be able to travel to the institute for data collection, have physician's clearance for moderate-vigorous exercise, and not be on other treatments.

Inclusion Criteria

You do less than 60 minutes of organized exercise each week.

Willing to travel to Dana-Farber Cancer Institute for necessary data collection

I am newly diagnosed with GVHD and starting high-dose corticosteroids for the first time since my transplant.

Exclusion Criteria

I do not have any uncontrolled illnesses like infections or diabetes.

I started my steroid treatment less than 7 days ago.

I have a condition affecting my muscles, bones, heart, or lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either an aerobic and resistance exercise program or a stretching program for 12 weeks

12 weeks

3 visits per week (virtual for exercise group), 4 testing visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of physical function, fitness, and patient-reported outcomes

13 weeks

Evaluations at week 13 and week 25

What Are the Treatments Tested in This Trial?

Interventions

• Attention control
• Exercise
• N/A

Trial Overview The RESTART Trial is testing if a home-based aerobic and resistance exercise program can reduce complications from corticosteroids in patients with GVHD compared to a control group doing stretching exercises. Participants will either follow the exercise regimen or the attention control stretching program.

How Is the Trial Designed?

Group I: Exercise Group Experimental Treatment 1 Intervention

Home-based, virtually supervised via Zoom, 3x weekly for 12-weeks aerobic and resistance exercise program Participants will also undergo four testing visits across 6-month period. Tests will include four blood draws and three body composition scans via a dual-energy x-ray absorptiometry (DXA).

Group II: Attention control Group Experimental Treatment 1 Intervention

Home-based, 12-week stretching program only with participants asked not to change their activity behavior. Participants will also undergo four testing visits across 6-month period. Tests will include four blood draws and three body composition scans via a dual-energy x-ray absorptiometry (DXA).

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

A study involving 26 participants, primarily with multiple myeloma, identified that many patients (50%) felt confident about exercising before hematopoietic stem cell transplantation (HSCT), but faced barriers such as lack of knowledge, inadequate support from healthcare providers, and emotional challenges related to their treatment.

To improve prehabilitation interventions, exercise programs should be tailored to individual needs, flexible in structure, and include educational components, with the suggestion that including exercise professionals in the care team could enhance support for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Preferences, Barriers, and Facilitators of Individuals With Cancer Undergoing Chemotherapy Before Stem Cell Transplantation: A Mixed-Methods Study. Purdy, GM., Nanad, R., Ternes, L., et al.[2023]

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is beneficial for patients with hematologic disorders, but it can lead to significant complications like acute and chronic graft-versus-host disease (GvHD), which negatively impact quality of life and survival.

Engaging in physical activity and exercise post-transplant can improve physical function and quality of life for patients, potentially offering benefits comparable to pharmacologic therapies, and should be integrated into care plans as early as possible after the transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients. Fiuza-Luces, C., Simpson, RJ., Ramírez, M., et al.[2018]

A study of 59 hematopoietic stem cell transplant recipients on glucocorticoid therapy showed that 54% were able to adhere to a 4-week exercise rehabilitation program, despite high rates of hospital readmission affecting adherence.

While the overall group did not show significant improvements in physical performance, 40% of those who completed the program experienced clinically significant gains, indicating that exercise rehabilitation can be beneficial for some patients in this high-acuity population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence of stem cell transplant recipients receiving glucocorticoid therapy to an exercise-based rehabilitation program. Morris, GS., Brueilly, KE., Scheetz, JS., et al.[2021]

An 11-week moderate-intensity exercise program significantly improved physical capacity in mice with acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation, indicating a potential therapeutic benefit.

In chronic graft-versus-host disease (cGVHD), exercise training helped maintain physical capacity over time, suggesting that exercise could be a valuable adjunct therapy for managing GVHD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise interventions in graft-versus-host disease models. Fiuza-Luces, C., González-Murillo, A., Soares-Miranda, L., et al.[2014]

A supervised exercise program during inpatient hospitalization for pediatric hematopoietic stem cell transplantation (HSCT) was found to be safe and well tolerated, with no negative impact on mortality or graft-related complications.

The exercise intervention was associated with a reduced incidence of total and viral infections in patients undergoing allogeneic HSCT, suggesting potential benefits for infection management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored Exercise during Hematopoietic Stem Cell Transplantation Hospitalization in Children with Cancer: A Prospective Cohort Study. Morales, JS., González Vicent, M., Valenzuela, PL., et al.[2020]

In a study involving a murine model of chronic graft versus host disease (cGVHD), a moderate-intensity exercise program significantly improved survival rates and reduced clinical severity scores in mice undergoing allogeneic hematopoietic stem cell transplantation.

The exercise regimen also enhanced physical fitness and positively influenced immune responses by increasing levels of certain lymphocytes and decreasing inflammatory cytokines, suggesting that exercise may be a beneficial intervention for patients with cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise benefits in chronic graft versus host disease: a murine model study. Fiuza-Luces, C., Soares-Miranda, L., González-Murillo, A., et al.[2017]

The IRENE-G study is a 24-week randomized controlled trial involving 112 GvHD patients, aiming to evaluate the effects of resistance exercise combined with nutritional support on physical performance and health outcomes, compared to nutritional support alone.

This study is the first of its kind to investigate how resistance training may help prevent muscle loss and improve physical function in GvHD patients, potentially offering a new approach to managing the side effects of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Resistance Exercise and Nutritional Endorsement on physical performance in patients with GvHD (IRENE-G study) - design and rational of a randomized controlled trial. Bujan Rivera, J., Kühl, R., Zech, U., et al.[2022]

In a study involving BALB/C female mice with chronic graft-versus-host disease (cGVHD), moderate-intensity treadmill exercise over 11 weeks improved cardiac function by enhancing autophagy markers in the heart, suggesting a protective mechanism against heart damage.

The exercise training led to increased levels of key proteins associated with autophagy and antioxidant defense, indicating that physical activity may help maintain heart health even in severe conditions like cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training can induce cardiac autophagy at end-stage chronic conditions: insights from a graft-versus-host-disease mouse model. Fiuza-Luces, C., Delmiro, A., Soares-Miranda, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9024288/

Impact of Resistance Exercise and Nutritional Endorsement ... Graft-versus-host disease (GvHD) remains a major complication and limitation to successful allogeneic hematopoietic stem cell transplantation.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666087321000193

Role of Physical Activity and Cardiac Rehabilitation in ... No significant favorable effects of a supervised high-intensity exercise program on physical fitness, fatigue, body composition, QoL, distress, or physical ...

3. astctjournal.org astctjournal.org/article/S2666-6367(24)00431-7/fulltext

Current Landscape and Future Directions Ongoing randomized trials studying the effects of exercise and nutrition on clinical outcomes in cGVHD and allo-HCT patients may provide important future ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05236062

Study Details | NCT05236062 | Impact of Exercise on the ... This study is about determining if an aerobic and resistance exercise intervention is feasible in patients diagnosed with acute or chronic GVHD ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4703521/

Physical function and quality of life in patients with chronic ... This review addresses how cGVHD affects patients' physical function and physical domain of QoL, and the potential benefits of exercise interventions.