Physical Therapy in Patients Undergoing Allo-HSCT With cGVHD

Physical Therapy in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation With a Diagnosis of Chronic Graft-versus-host Disease: A Randomized Clinical Trial.

Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) represents the only curative option for many patients diagnosed with various hematologic neoplasms. Procedure-related morbidity and mortality pose challenges to long-term outcomes and quality of life, especially among patients who develop chronic graft-versus-host disease (cGVHD). There is a gap in healthcare that comprehensively addresses the specific needs of these patients. Physical therapy as an adjuvant treatment, through therapeutic exercise involving muscle strength and cardiorespiratory endurance, has shown positive influences on health markers and serves as a strong medical ally in similar profiles. Although these strategies could be reproducible and potentially beneficial for cGVHD patients, research has been limited to date, with the role of physical therapy possibly underutilized in this field. Justification: Unaddressed medical gap with no rigorously scientific responses specific to cGVHD. Objectives: This project aims to conduct the first randomized clinical trial from a physical therapy perspective as an adjuvant treatment for patients undergoing alloHSCT diagnosed with cGVHD.

Study Overview

• Status: Not yet recruiting
• Conditions: Stem Cell Transplant Complications; Graft-versus-host-disease; Hematological Malignancy; Hematologic Cancer; Graft Versus Host Disease, Chronic
• Intervention / Treatment: Other: Physical therapy

Detailed Description

Design: Prospective controlled clinical trial.

Location: Virgen del Rocío University Hospital, Hematology Unit.

Statistical analysis plan:The data will be analyzed using SPSS v.26 software for Windows and Epidat 4.2. All statistical tests will be conducted considering a 95% confidence interval (p-value <0.05). To compare the score of the main outcome measure, quality of life (score range 0-200), between the experimental and control groups, the t-test or Mann-Whitney test will be employed (depending on the normality of the data). The comparison will be conducted at three time points (T0, T1, and T2). Furthermore, multivariate analysis will be performed using generalized equations of repeated measures to determine score changes between the groups. Since it is a Likert scale-based score, the Friedman test will be used to compare score changes, employing the Bonferroni test for pairwise comparisons.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raquel P Aguilar, PhDcand; Phone Number: +34 955 013 260; Email: raquelijorml@gmail.com
• Study Contact Backup: Name: José Antonio P Simón, PHD; Phone Number: +34 955 013 260; Email: josea.perez.simon.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Seville, Spain, 41013
    • University of Seville; Manuel Siurot Avenue, no number
    • Contact: Raquel P Aguilar, Ph.D.cand.; Phone Number: 34 955 013 260; Email: raquelijorml@gmail.com
    • Contact: José Antonio P Simón, PhD; Phone Number: 34 955 013 260; Email: josea.perez.simon.sspa@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with chronic Graft-Versus-Host Disease (cGVHD) treated at Virgen del Rocío University Hospital will be invited to participate in the trial (n=108), under the following eligibility criteria: Inclusion criteria:
• Adult (18 years or older); Underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) diagnosed with cGVHD; No medical contraindication for moderate or high-intensity exercise; Proficiency in the Spanish language; Have access to the internet.

Exclusion Criteria:

• Unable to perform initial or final physical assessments; Having serious pre-existing conditions before the oncological diagnosis or diseases that are not or poorly controlled; Not signing or delivering the informed consent on the indicated date.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Participants from both groups will undergo the three assessments and receive standard medical care.The patients in the experimental group will participate, at Time T1 (week 1 to 12), in a 12-week physiotherapy treatment program consisting of a total of 38 sessions: 2 health education sessions, 24 supervised combined exercise sessions, and 12 self-administered complementary exercise sessions.	Other: Physical therapy; Health education sessions and combined therapeutic exercise sessions, based on muscular strength training and cardiorespiratory endurance.
No Intervention: Control group; Participants from both groups will undergo the three assessments and receive standard medical care. The Control Group (GC), externally to the trial itself, for ethical reasons, considering potential benefits without risks, and as a strategy for blinding the study itself, will carry out the physiotherapy treatment program following the final assessment of the study, becoming a hybrid program under the same protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	MEASURE NAME: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT); VERSION: 4; NUMBER OF ITEMS: 50; RESPONSE SCALE: 5 point Likert-type scale; SCORING:Manual scoring template, some items are reverse scored. Higher score represents better quality of life.	Week 1, Week 6, and Week 13
Chronic Graft-Versus-Host Disease (cGVHD) symptom burden	Modified Lee Chronic Graft-Versus-Host Disease Symptom Scale (mLSS) for 7 days. This is an instrument with 7 domains (skin, eyes, mouth, lungs, nutrition, energy, and psychiatry) and a total of 28 items to assess. The response options for "Please inform us if any of the following problems have bothered you in the last 7 days" range from 0 to 4 (Not at all, A little, Moderately, Quite a bit, Extremely). A difference of 5 to 6 points (standard deviation) will be considered clinically significant. Subscales range from 0 to 100, with a higher score indicating worse symptoms.	Week 1, Week 6, and Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular strength	Sit-to- Stand test y Handrig strength test	Week 1, Week 6, and Week 13
Cardiorespiratory fitness	2-min Walk Test	Week 1, Week 6, and Week 13
Functional status	Human Activity Profile (HAP)	Week 1, Week 6, and Week 13
Distress	Distress-Thermometer	Week 1, Week 6, and Week 13
Mood	"Mood Assessment Scale" (MAS); Designed to assess transient mood states, both positive and negative, in any individual at any time, through 16 items divided into four scales (depression, anxiety, hostility, and joy), each defined by 4 items and evaluated using the Likert scale, with scores ranging from 0 to 10. The values for each category are calculated by the mean. All 16 statements have the same structure; they all begin with the phrase "I feel" and end with an adjective describing a mood state.	Week 1, Week 6, and Week 13
Anxiety	Hospital Anxiety and Depression Scale (HADS) questionnaire; The "Hospital Anxiety and Depression Scale questionnaire" (HADS); a useful tool for identifying anxiety and depression states in cancer patients and applicable during clinical practice. The two categories consist of one subscale each, with seven items rated from 0 to 4 points, with higher scores (in the range of 0 to 21) indicating anxious and depressive states. Participants should respond considering how they felt and/or behaved during the last seven days.	Week 1, Week 6, and Week 13
Biological markers	Cytokines (interleukins) and lymphocytic populations as part of routine analysis. Blood sample.	Week 1, Week 6, and Week 13
Responses to medical treatment	NIH Criteria	Week 1, Week 6, and Week 13

Collaborators and Investigators

• Sponsor: University of Seville
• Investigators: Study Director: José Antonio P Simón, PHD, Chief of Hematology at Virgen del Rocío University Hospital.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: February 25, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Rehabilitation; Exercise; Physical therapy; Physiotherapy; Graft versus host disease; Hematopoietic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Hematologic Neoplasms; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: ECA GVHD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol for a randomized clinical trial.
• IPD Sharing Time Frame: When the study concludes; estimating by the end of the year 2025
• IPD Sharing Access Criteria: Both the study protocol and results, as well as the statistical plan, will be published in journals registered in the Journal Citation Report
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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