Investigating the Role of Energy Balance Modification on Health Responses in Chronic Lymphocytic Leukaemia (HIT-CLL)

This randomised control clinical trial aims to investigate the effects of exercise training and diet on physical and functional fitness and immunological and metabolic changes in adults with chronic lymphocytic leukaemia. Investigators will randomise participants to either 12 weeks of supervised/semi-supervised exercise only, exercise + nutritional guidance, or no exercise.

Study Overview

• Status: Recruiting
• Conditions: Frailty; Chronic Lymphocytic Leukemia; Muscle Function; Immune Function; Lipid Cell; Tumor
• Intervention / Treatment: Behavioral: HIT; Behavioral: EXE+ Nutritional Guidance

Detailed Description

This study aims to perform a randomised control trial of exercise or exercise plus nutritional guidance on the physiological and immunological health of adults diagnosed with chronic lymphocytic leukaemia (CLL). Recruited participants will be randomised to either 12 weeks of an exercise-only program, an exercise-plus nutritional guidance program or a no-exercise control group. Fasting blood samples collected at Baseline and 12 weeks will measure absolute CLL cell counts, immune function, and inflammatory and metabolic biomarkers. A series of physical fitness assessments will be assessed at baseline and 12 weeks to determine physiologic reserve and resilience against external stressors. Additionally, participants will be asked to return 12 weeks after completing the intervention to assess the legacy effects of the intervention on the same physiological and blood-based biomarkers of health.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David Bartlett, PhD; Phone Number: 01483 683 245; Email: d.bartlett@surrey.ac.uk
• Study Contact Backup: Name: Ellie Miles; Phone Number: 01483 688 559; Email: e.e.miles@surrey.ac.uk

Study Locations

• United Kingdom
  • Guildford, United Kingdom, GU2 7WG
    • Recruiting
    • University of Surrey
    • Contact: David Bartlett, PhD; Phone Number: 01483 683 45; Email: d.bartlett@surrey.ac.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Confirmed diagnosis of CLL (including small lymphocytic leukaemia) as per the International Workshop on CLL Guidelines.
• Male or female ≥ 18 years of age
• Able to walk on a treadmill or cycle on an ergometer
• Pass the Physical Activity Readiness Questionnaires (PAR-Q and PAR-Q+)

Exclusion Criteria:

• Corticosteroid therapy initiated less than 7 days before study entry. Prednisone 10mg or less or equivalent is allowed. Topical or inhaled corticosteroids are permitted.
• Secondary malignancy within 3 years of study enrollment requiring intervention except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localised prostate cancer and PSA stable.
• Absolute contraindications to exercise: Recent (<6 months) acute cardiac event unstable angina, uncontrolled dysrhythmias causing symptoms or hemodynamic compromise, symptomatic aortic stenosis, uncontrolled symptomatic heart failure, acute pulmonary embolus, acute myocarditis or pericarditis, suspected or known dissecting aneurism and acute systemic infection.
• Significant orthopaedic limitations, musculoskeletal disease and/or injury. Due to the nature of the study, persons with known joint, muscle or other orthopaedic limitations that restrict physical activity may be excluded.
• Type I diabetes mellitus or uncontrolled Type II diabetes mellitus, or chronic obstructive pulmonary disease
• Uncontrolled blood pressure (≥180/90) at rest
• Known concurrent HIV, Hepatitis B or Hepatitis C
• Unable to comply with other study requirements

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIT Group; Exercise Only; 3 sessions per week; Aerobic + Resistance Exercises	Behavioral: HIT; Exercise training only
Experimental: EXE+ Group; Exercise + Nutritional Guidance; 3 sessions per week; Aerobic + Resistance Exercises; Dietary assessment at baseline and during with guidance on eating a healthy diet provided	Behavioral: EXE+ Nutritional Guidance; Exercise Training + Nutritional Guidance
No Intervention: Control Group; Control group will receive no exercise or nutritional guidance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in absolute number of CD19+/CD5+ CLL cells at week 12	A blood sample will be taken and assessed for CD19+/CD5+ CLL frequency using flow cytometry and total lymphocyte counts to determine the absolute number of CLL cells in x10^9/L	Baseline and 12 weeks
Change from baseline in cardiorespiratory fitness (CRF: VO2peak) at week 12	Cardiopulmonary exercise testing will be conducted to assess changes in fitness	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frailty	Frailty will be determined by a series of validated physical function tests that provide a score of 0-1(Robust), 2 (Pre-Frail), 3-5 (Frail)	Baseline and 12 weeks
Muscle Strength and Endurance	Estimated one repetition maximum and repetitions to failure using machine-based weights	Baseline and 12 weeks
Muscle Health	Ultrasound and near-infrared spectroscopy assessment of muscle fuel usage	Baseline and 12 weeks
Change in Quality of Life using the EORCT-QLQ-C30	Quality of life will be determined by the EORCT-QLQ-C30 questionnaire	Baseline and 12 weeks
Change in B-CLL Cell Function	Measurement of in vitro B-CLL cell proliferation by flow cytometry	Baseline and 12 weeks
Change in muscle oxygen metabolism during a single bout of exercise	Measurement of muscle oxygenation via near infrared spectroscopy during a single session of acute exercise	Baseline and 12 weeks
Change in systemic and cellular bioenergetics	Measurement of in vitro immune cell fuel utilisation by high resolution respirometry and mass spectrometry	Baseline and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Legacy Effect of Intervention on absolute number of CD19+/CD5+ CLL cells	Reassessment of absolute number of CD19+/CD5+ CLL cells following 12 weeks of unguided exercise training	12 weeks to 24 weeks
Legacy Effect of Intervention on change in cardiorespiratory fitness (VO2peak) as measured by a cardiopulmonary exercise test	Reassessment of CRF following 12 weeks of unguided exercise training	12 weeks to 24 weeks

Collaborators and Investigators

• Sponsor: University of Surrey
• Collaborators: American Society of Hematology
• Investigators: Principal Investigator: David Bartlett, PhD, University of Surrey

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Leukemia; Frailty; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: FHMS 21-22 263 EGA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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