Clinical trial NCT05111834: IRENE-G Study: Impact of Resistance Exercise and Nutritional Endorsement on GvHD Symptoms
Official title: IRENE-G Study: Impact of Resistance Exercise and Nutritional Endorsement on GvHD Symptoms
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Graft Vs Host Disease
Keywords: Resistance Training
Nutritional Endorsement
Allogenic stem cell transplantation
Steroid-induced myopathy
Cancer
Exercise
Graft versus host disease
Physical performance
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: Deutsche José Carreras Leukämie-Stiftung
First posted: 2021-11-08
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The IRENE-G trial is a randomized controlled study that aims to investigate the effect of a supervised resistance exercise program (2x/week for 24 weeks) in combination with a nutritional intervention on physical performance/frailty in patients with GvHD symptoms treated with high dose steroids.

Detailed description: Graft-versus-host disease (GvHD) remains the major complication and limitation to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment of GvHD is challenging, with high-dose steroids remaining the established first-line treatment in both acute and chronic GvHD. Long-term doses of systemic corticosteroids have many well-known side-effects such as myopathy, though often an overlooked diagnosis. Previous studies in non-cancer patients treated with corticosteroids demonstrated that resistance training can reverse muscle atrophy and weakness. Despite the beneficial effects of exercise, no research effort to date has explicitly examined the effect of a progressive moderate-to-high intensity resistance training on the physical performance and well-being of GvHD patients treated with high-dose steroids. As GvHD patients are commonly found to be malnourished, which affects muscle mass and strength and thus quality of life, nutritional endorsement and optimization should be considered when investigating the effect of exercise in GvHD patients.

The IRENE-G study (acronym for Impact of Resistance Exercise and Nutritional Endorsement on GvHD symptoms) is a 24 week prospective, randomized controlled intervention trial with a two-armed parallel design and 1:1 allocation ratio of GvHD patients treated with high-dose steroids.The exploratory study examines and compares the effects of a supervised resistance exercise intervention - 2x per week, 60 minutes - and a nutritional optimisation program (experimental group) against a nutritional optimisation program only (control group) on physical performance in GvHD patients treated with high-dose steroids. We hypothesize that patients in the experimental group will show significantly greater improvements (or an attenuated decrement) in their physical performance after 24-weeks compared to the control group. Moreover, the investigators hypothesized that the experimental group will have lower levels of fatigue, a higher perceived quality of life, better muscle strength values and a higher vastus lateralis muscle volume, a better nutritional status as well as a better submaximal endurance capacity compared to the control group.

On the basis of power calculations, the goal is to include 56 patients per intervention arm, resulting in a total patient number of n=112.

Assessments will take place at week 8, 16 and 24 after baseline. A follow-up assessment is planned at week 48.

The primary outcome of IRENE-G is physical performance measured via the Short Physical Performance Battery. Further endpoints are muscle strength and volume, submaximal endurance capacity, nutritional status and patient-reported outcomes such as quality of life and fatigue.

Eligibility criteria: Inclusion Criteria:

* Existing or new diagnosis of acute or chronic GvHD treated with systemic steroid therapy (≥0,5 mg/kg/day)
* Sufficient German language skills
* Willing/ able to train at the provided exercise facilities or online twice a week
* Willing/ able to take part in the scheduled testing
* Capacity to consent
* Signed informed consent

Exclusion Criteria:

* Any physical or mental conditions that would hamper the adherence to the training and/or nutritional program or the completion of the study procedures
* Heart insufficiency \> NYHA III or uncertain arrhythmia
* Uncontrolled hypertension
* Severe renal dysfunction (GFR \< 30%, Creatinine\> 3mg/dl)
* Reduced standing or walking ability
* Insufficient hematological capacity (either hemoglobin value below 8 g/dl or thrombocytes below 30.000/µL)
* Any other comorbidities that preclude participation in the exercise programs

Primary outcomes:
measure: Change from baseline to week 24 in Physical performance, as measured by the Short Physical Performance Battery (SPPB)
timeFrame: up to 24 weeks (& 6 month follow-up)
Secondary outcomes:
measure: Change from baseline to week 24 in Submaximal endurance performance, assessed with the 6 minute walk test
timeFrame: up to 24 weeks (& 6 month follow-up)
measure: Change from baseline to week 24 in Muscle strength performance, as measured by Hand-held dynamometer
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in Muscle volume, assessed with ultrasound measurement
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in Nutritional Status
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 Health related Quality of life, as measured by the EORTC QLQ-C30
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in high-dose chemotherapy and stem cell transplantation-related symptoms and problems, as measured by the EORTC QLQ-HDC 29
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in Cancer-related Fatigue, as measured by the EORTC QLQ-FA12
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in patient-perceived GVHD symptom bother, as measured by the modified 7-day Lee Chronic-versus-Host Disease Symptom Scale
timeFrame: up to week 24 (& 6 month follow-up)
measure: Change from baseline to week 24 in Functional Status determined with the Karnofsky performance scale
timeFrame: up to week 24 (& 6 month follow-up)
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital
Study officials:
affiliation: Heidelberg University Hospital, National center for Tumor Diseases, Division of Medical Oncology
name: Joachim Wiskemann, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bujan Rivera J, Kuhl R, Zech U, Hendricks A, Luft T, Dreger P, Friedmann-Bette B, Betz TM, Wiskemann J. 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. BMC Cancer. 2022 Apr 22;22(1):440. doi: 10.1186/s12885-022-09497-1.