Impact of Exercise on the Complications of Corticosteroids in Patients With GVHD: the RESTART Trial (RESTART)

Impact of Exercise on the Complications of Corticosteroids in Patients With Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplantation: the RESTART 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

Study Overview

• Status: Recruiting
• Conditions: Graft Vs Host Disease; Acute-graft-versus-host Disease; Chronic Graft-versus-host-disease
• Intervention / Treatment: Behavioral: Exercise; Behavioral: Attention control

Detailed Description

This research study is a feasibility study, which is the first-time investigators are examining an aerobic and resistance exercise (A+R) in patients diagnosed with acute or chronic GVHD after having an allogeneic stem cell transplant and if participating in a specific exercise program can improve glycemic control, body composition, physical fitness and function, and patient-reported outcomes.

This study consists of participants randomly assigned in 2(A+R):1(AC) ratio to one of two groups:

• Aerobic and resistance exercise (A+R), or
• Attention control (AC)

The A+R group will be asked to perform aerobic exercise, which can improve cardiovascular (heart) and lung function, and resistance exercise (e.g., dumbbell lifting), to help build muscle mass and strength. The AC group will be asked to perform stretching only and not to change their activity behavior.

All participants will also undergo four testing visits involving four blood draws and three body composition scans via a dual-energy x-ray absorptiometry (DXA).

Participants will be in this research study for 6 months.

It is expected that about 36 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christina Dieli-Conwright, PhD, MPH; Phone Number: 617-582-8321; Email: ChristinaM_Dieli-Conwright@dfci.harvard.edu
• Study Contact Backup: Name: Jordan Lane, MS; Phone Number: 617-582-7494; Email: jordan_lane@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Christina Dieli-Conwright, PhD, MPH
      • Contact: Christina Dieli-Conwright, PhD, MPH; Phone Number: 617-582-8321; Email: ChristinaM_Dieli-Conwright@dfci.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Christina Dieli-Conwright, PhD
      • Contact: PhD, MPH
      • Contact: Christina Dieli-Conwright, PhD, MPH; Phone Number: 617-632-3800; Email: ChristinaM_Dieli-Conwright@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Over 18 years old; children under the age of 18 will be excluded due to rarity of disease
• Newly diagnosed with acute or chronic GVHD, starting corticosteroids at a dose of .20 mg/kg or greater for the first time since transplant
• Received allogeneic stem cell transplant (any conditioning, any donor) at Dana-Farber Cancer Institute
• Physician's clearance to participate in moderate-vigorous intensity exercise
• Speak English
• Currently participate in less than 60 minutes of structured exercise/week
• Willing to travel to Dana-Farber Cancer Institute for necessary data collection
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Have a plan for hospital admission within the next 13 weeks at the time of recruitment
• If patients are not enrolled within 14 days after initial steroid treatment, they will be ineligible
• Pre-existing musculoskeletal or cardiorespiratory conditions
• Patients should not have any uncontrolled illness including ongoing or active infection, uncontrolled diabetes, hypertension, or thyroid disease
• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
• Patients with other active malignancies
• Participate in more than 60 minutes of structured exercise/week
• Unable to travel to Dana-Farber Cancer Institute for necessary data collection
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Group; 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).	Behavioral: Exercise; aerobic and resistance exercise
Experimental: Attention control Group; 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).	Behavioral: Attention control; stretching

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients completing the exercise intervention sessions	The primary outcome is feasibility and will be assessed by the proportion of patients completing the exercise intervention sessions with >70% completion considered feasible.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control level	Glycemic control level change will be measured by Homeostasis Model Assessment (HOMA). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Body Composition	Body Composition Index change will be measured by Dual Energy X-Ray Absorptiometry (DEXA). Differences in lean mass, fat mass, and body fat % between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Cardiopulmonary Fitness	Cardiopulmonary fitness will be measured by a submaximal graded exercise cycling test. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Physical function - Margaria Stair Climb	Functional power will be measured using the Margaria Stair Climb test. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Physical Fitness	Physical Fitness will be measured by the short physical performance battery (SPPB). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Physical Function - Handgrip Strength	Handgrip strength will be measured by a hand-held dynamometer. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Physical Function - Timed Up and Go	Physical function will be assessed with the timed-up-and-go (TUG) test. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Physical Function - 6 minute walk test	Physical function will be assessed with the 6 minute walk test (6MWT). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Muscular Strength	Muscular strength will be assessed with a 10 repetition maximum test. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Patient reported outcomes - Fatigue	Fatigue will be measured by the PROMIS cancer fatigue short form. Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Patient reported outcomes - Function	Function will be measured by the Vulnerable Elders Survey (VES). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Patient reported outcomes - Quality of Life	Quality of life will be assessed by the functional assessment of cancer therapy - bone marrow transplant (FACT-BMT). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Patient reported outcomes - Anxiety and Depression	Anxiety and depression will be assessed by the Hospital Anxiety and Depression Scale (HADS). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI. The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains. Patients were defined as having anxiety or depression or both if the score was 8 or more in the corresponding subscale.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up
Patient reported outcomes - Sleep	Sleep will be assessed by the Pittsburg sleep quality index (PSQI). Differences between post- and pre-intervention will be assessed using paired t-test or Wilcoxon signed-rank test. For binary outcomes, it will be a calculation of the proportion and corresponding 95% exact CI.	Evaluated at week 1 at baseline and week 7 on treatment, and at week 13 post-treatment also at week 25 follow-up

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Christina Dieli-Conwright, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): September 9, 2026
• Study Completion (Estimated): September 9, 2027

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Allogeneic stem cell transplant; Corticosteroids; Graft Vs Host Disease; Acute-graft-versus-host Disease; Chronic Graft-versus-host-disease
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: 21-618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No