Lifestyle-modifying Interventions in Low-risk MDS Patients (MDS-LIME)

Prospective Evaluation of Lifestyle-modifying Interventions on Disease Parameters, Inflammatory and Metabolic Processes in Low-risk MDS Patients

Myelodysplastic syndromes (MDS) are acquired clonal stem cell diseases characterized by hematopoietic cell dysplasia, cytopenia, and the risk of progression to acute myeloid leukemia. In addition to clonal changes in the hematopoietic stem and progenitor cells itself, growing evidence suggests that inflammatory and metabolic changes in the bone marrow microenvironment play an important role in disease development and maintenance of the malignant clone. The positive impact of dietary interventions (e.g. fasting) and physical activity on inflammation and metabolic parameters could be shown in various benign inflammatory disease entities (e.g. atherosclerosis, chronic renal insufficiency, cystic fibrosis etc.).

The aim of this study is to describe the hematological, metabolic, inflammatory, and microbiological changes after combined lifestyle-modifying interventions (outpatient physiotherapy and fasting mimicking diet (FMD) in patients with low-risk MDS.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Other: Fasting-mimicking diet (FMD) and physiotherapy

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

Contacts and Locations

• Study Contact: Name: Ekaterina Balaian, Dr.; Phone Number: +4935145819493; Email: Ekaterina.Balaian@ukdd.de
• Study Contact Backup: Name: Katja Sockel, Dr.; Phone Number: +4935145815627; Email: katja.sockel@ukdd.de

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18-75 years of age
2. Cytomorphologically confirmed MDS or MDS/MPN according to WHO criteria (incl. MDS-RARS-T, CMML)
3. IPSS-R very low, low, or intermediate
4. Hemoglobin <11 g/dL (6.8 mmol/l)
5. Non-transfusion dependent (NTD) per IWG 2018 criteria (≤2 blood transfusions within 16 weeks prior to inclusion in the study)
6. ECOG≤2
7. Body mass index (BMI) ≥ 20 kg/m2
8. Written informed consent of the subject after clarification

Exclusion Criteria:

1. AML
2. MDS IPSS-R high or very high
3. History of HSCT
4. MDS-specific drug therapy (including erythropoietin, erythropoiesis-modulating agents, lenalidomide, iron chelation, hypomethylating agents) ongoing or planned in the next 6 months
5. Diabetes mellitus requiring therapy or any other known metabolic disease
6. Application of systemic cortisone-containing drugs
7. Known psychiatric eating disorder (e.g. anorexia nervosa, bulimia)
8. Physical inability to follow the physical and/or nutritive interventions
9. simultaneous participation in another interventional clinical trial (including within the last 4 weeks before inclusion)
10. addictions or other illnesses that do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences
11. pregnant or breastfeeding women
12. indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMD first; Patients receive nutritional counselling on the principles of the FMD diet and individual recommendations for optimising the micronutrient balance (vitamins, trace elements) based on their corresponding baseline values. A food diary is given to the patients to assess treatment adherence on FMD days. This is followed by a combined nutritive and physiotherapeutic interventions from week 13 for a further 3 months. Patients will be instructed about ambulatory exercises during a physiotherapeutic counselling, scheduled in week 13. Physiotherapy exercises should only be carried out on FMD-free days. Patients also receive a diary in which they document daily physical activity.	Other: Fasting-mimicking diet (FMD) and physiotherapy; FMD is a diet held monthly during five days with the restriction of calories to less than 1000 kcal, glucose and proteins. Physiotherapy will be organized as home-based exercises explained by the physiotherapeutist at the beginning of the study.
Experimental: Physiotherapy first; Patients receive physiotherapy counselling, with structured ambulatory exercises shown and explained. The patients receive a diary where they have to document their physical activity every day. This is followed by a combined nutritive and physiotherapeutic interventions from week 13 for a further 3 months. For this purposphe, nutritional counselling on the principles of the FMD diet is planned for week 13. In addition, individual recommendations for optimising the micronutrient balance (vitamins, trace elements) are given based on the respective baseline values. The physiotherapeutic exercises are to be carried out only on FMD-free days. Patients will also be given a food diary to assess treatment adherence on FMD days.	Other: Fasting-mimicking diet (FMD) and physiotherapy; FMD is a diet held monthly during five days with the restriction of calories to less than 1000 kcal, glucose and proteins. Physiotherapy will be organized as home-based exercises explained by the physiotherapeutist at the beginning of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematological improvement	Hemoglobin level at the EOT visit, g/dL	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of a priori metabolic parameters of MDS patients after combined physiotherapeutic and nutritive interventions	Panel measurement, mg/dL	6 months
Evaluation of a priori inflammatory parameters of MDS patients after combined physiotherapeutic and nutritive interventions	Panel measurement, ng/mL	6 months
Patients' adherence to therapy as an expression of the relevance of the lifestyle-modifying interventions in everyday life	Diary analysis	6 months
Impact on quality of life	QUALMS questionnaire	6 months
Impact on fatigue	Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score	6 months

Collaborators and Investigators

• Sponsor: Technische Universität Dresden

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): April 1, 2026
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: inflammation; physiotherapy; metabolism; Myelodysplastic syndrome; lifestyle modification; fasting-mimicking diet
• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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