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

Trial Summary

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 data supports the effectiveness of the treatment for Exercise for Graft-versus-Host Disease?

Research shows that exercise can improve physical fitness, quality of life, and reduce disease progression in patients with chronic graft-versus-host disease (cGVHD). Exercise interventions have been found to be safe and may decrease the risk of infections in patients undergoing hematopoietic stem cell transplantation. ^{1 2 3 4 5}

Is exercise safe for people with graft-versus-host disease?

Exercise is generally safe for people with graft-versus-host disease (GVHD) and does not increase the risk of mortality or complications like graft failure. In fact, it may help reduce infections and improve physical capacity. ^{1 2 4 5 6}

How does exercise as a treatment for graft-versus-host disease differ from other treatments?

Exercise is unique because it enhances physical fitness and quality of life without the side effects of drugs, and it can be as effective as medication in some cases. It works by improving physical capacity and potentially inducing beneficial cellular processes like autophagy, which helps maintain heart health in chronic conditions. ^{3 4 5 7 8}

What is the purpose of this trial?

This study is about determining if an aerobic and resistance exercise intervention is feasible in patients diagnosed with acute or chronic GVHD (Graft-Versus-Host Disease) after having an allogeneic stem cell transplant. The names of the study interventions involved in this study are: * Aerobic and resistance exercise (A+R) - Home-based aerobic and resistance exercise program * Attention control (AC) - Home-based stretching program

Research Team

Christina M Dieli-Conwright, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Tailored Exercise during Hematopoietic Stem Cell Transplantation Hospitalization in Children with Cancer: A Prospective Cohort Study. [2020]

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

Exercise Preferences, Barriers, and Facilitators of Individuals With Cancer Undergoing Chemotherapy Before Stem Cell Transplantation: A Mixed-Methods Study. [2023]

3. England 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. [2018]

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

Exercise benefits in chronic graft versus host disease: a murine model study. [2017]

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

Effects of exercise interventions in graft-versus-host disease models. [2014]

6. England 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Adherence of stem cell transplant recipients receiving glucocorticoid therapy to an exercise-based rehabilitation program. [2021]

8. Netherlands 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. [2022]