Exercise As Intervention in Chronic Lymphocytic Leukemia (ADRENALINE)

Randomised Controlled Clinical Trial of Exercise As Intervention in Chronic Lymphocytic Leukemia

PURPOSE: The purpose of the study is to determine the effects of 16-weeks of exercise training, as measured by aerobic capacity, strength and physical function, and body composition, in patients with Chronic Lymphocytic Leukemia (CLL).

DESIGN: Subjects will have confirmed treatment naïve CLL. Subjects will be assigned to either a 16-week control group (no supervised exercise) or an intervention group of Resistance Training (REx). Before and after the 16-week protocol, patients will undergo several tests including: 1) a maximal cycle ergometer test, 2) Body Composition, 3) Muscle strength, 4) physical activity levels, 5) blood measures (e.g. immune and inflammatory functions).

DATA ANALYSES & SAFETY ISSUES: For outcomes, group change differences from baseline to 16-weeks will be compared with ANCOVA. Resistance training is a very safe exercise modality already studied in other cancer patients. The regular use of vigorous-intensity exercise has been used extensively in exercise training. It will always be respected for each subject's safety tolerance while challenging.

HYPOTHESIS: The investigators hypothesize that the protocol will be feasible exercise interventions for people with CLL and will improve health and fitness markers.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Behavioral: Exercise Training as Intervention

Detailed Description

PURPOSE: The purpose of the study is to determine the effects of 16-weeks of exercise training, as measured by aerobic capacity, strength and physical function, and body composition, in patients with CLL and without any prior treatment.

DESIGN: Subjects will have confirmed treatment naïve CLL. Subjects will be assigned to either a 16-week control group (no supervised exercise) or an intervention group of Resistance Training (REx). Before and after the 16-week protocol, patients will undergo several tests including: 1) a Cardiopulmonary Exercise Test with Electrocardiogram (CPET+ECG) maximal cycle ergometer test, 2) a dual-energy X-ray absorptiometry (DEXA) Body Composition test, 3) a Muscle strength test with dynamometry, 4) a characterization of physical activity (PA) levels with accelerometry, and 5) blood measures (e.g. immune and inflammatory functions). The REx group will undertake a strength-based type of training with intensities near 80% of 1-Repetition Maximum (1-RM), with individual supervision (personal training approach).

DATA ANALYSES & SAFETY ISSUES: For outcomes, group change differences from baseline to 16-weeks will be compared with ANCOVA. Resistance training is a very safe exercise modality already studied in other cancer patients. The regular use of vigorous-intensity exercise has been used extensively in exercise training. It will always be respected for each subject's safety tolerance while challenging.

HYPOTHESIS: The investigators hypothesize that the protocol will be feasible exercise interventions for people with CLL and will improve health and fitness markers. It is also expected to have a positive correlation between physical fitness improvement and blood and immunologic parameters.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Porto, Portugal, 4200-450
    • Faculty of Sport of University of Porto

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Confirmed diagnosis of CLL as per the International Workshop on CLL Guidelines
• No history of previous treatment of CLL
• Able to walk on a treadmill or cycle ergometer
• Able to carry weights, or use weight machines
• Pass initial evaluations (CPET for cardiac health, Isokinetic for muscular health)
• Willing to adhere to the exercise program
• Signed informed consent

Exclusion Criteria:

• Previous CLL treatments
• Ongoing engagement in a regular exercise program
• Indication of disease progression and for starting treatment within 6 months
• Other primary tumour
• Inability to perform exercise (Heart disease, advanced stage respiratory, renal, hepatic, neurological, or osteoarticular disease)
• Unable to travel to FADEUP facilities or comply with other study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resistance Exercise Training; Patients in the REx program are submitted to resistance machine exercises for the major muscle groups aiming to achieve the intensity of 80% of 1-Repetition Maximum (1-RM). A warmup and cool down of 10 and 5 minutes, respectively, were included in each session aiming workloads of 60%-85% of peak heart rate (HRp). Enrolment through the REx program resistance machines will be conducted from major muscle groups to minor muscle groups, from polyarticular to monoarticular exercises, and alternating between agonist and antagonist contraction according to the following laydown: Leg Press -> Leg Curl -> Leg Extension -> Chest Press -> Latissimus Pulldown -> Shoulder Press -> Triceps Extension -> Biceps Curl -> Abdominal Crunch.	Behavioral: Exercise Training as Intervention; Supervised Exercise Training as an Intervention using Resistance Training.
No Intervention: Conventional Care (Control Group); Control group patients received advice to follow their habitual physical activity routines and are contacted bimonthly to ensure participant retention in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VO2 peak as measured by cardiopulmonary exercise test	Cardio metabolic CPET + Stress ECG	Baseline to 16-weeks
Change in muscular strength (peak torque and power) as measured by isokinetic dynamometer exercise test	BIODEX Concentric/Concentric Strength Test for Lower Body evaluation	Baseline to 16-weeks
Change in muscular strength (grip force in kg) as measured by dynamometer exercise test	JAMAR Hand Grip for Upper Body Evaluation	Baseline to 16-weeks
Change in muscular strength (kg of weight lifted) as measured by 1 repetition maximum exercise test	1 Repetition Maximum For Strength Evaluation of Whole Body	Baseline to 16-weeks
Change in Whole Body Composition (comprehending grams of total mass, total fat mass, total lean mass and percentage of fat mass)	DEXA Test for Whole Body Composition	Baseline to 16-weeks
Change in Bone Mineral Density (comprehending Total Femural and Femural Neck bone mineral density)	DEXA Test for Bone Mineral Density	Baseline to 16-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Health Related Quality of Life as measured by FACIT-F questionnaire	Questionnaire The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), a 40-item measure that assesses self-reported fatigue.	Baseline to 16-weeks
Change in Health Related Quality of Life as measured by EORTC QLQ-C30 and CLL17 questionnaires	Questionnaire from EORTC Quality of Life Group (EORTC QLQ-C30) a 30-item instrument designed to measure quality of life in all cancer patients, with the supplement of CLL17 a 17-item instrument designed to measure quality of life in chronic lymphocytic leukemia patients	Baseline to 16-weeks
Change in Physical Activity patterns as measured by Accelerometry over a period of seven consecutive days	GT9XLink accelerometer from Actigraph to collect data of the Physical Activity patterns, over a period of seven consecutive days, with a minimum of 10 hours of daily assessment	Baseline to 16-weeks
Change in Blood counts (hemoglobin (g/dL) and platelets (10^9/L)) as measured by Peripheral Blood Collection	Peripheral Blood Collection during Hospital Consultation	Baseline to 16-weeks
Change in Leukocytes counts (in percentage of lymphocytes, monocytes, neutrophils) as measured by Peripheral Blood Collection	Peripheral Blood Collection during Hospital Consultation	Baseline to 16-weeks
Change in Minerals counts (comprehending iron (ug/dL), sodium (mEq/L), potassium (mEq/L) and magnesium (mEq/L)) as measured by Peripheral Blood Collection	Peripheral Blood Collection during Hospital Consultation	Baseline to 16-weeks

Collaborators and Investigators

• Sponsor: Universidade do Porto
• Collaborators: Research Centre in Physical Activity, Health and Leisure
• Investigators: Principal Investigator: Pedro MP Cunha, MSc., Faculty of Sport of University of Porto

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Physical Activity; Chronic Lymphocytic Leukemia; Strength Training; Vigorous Physical Activity
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: CLL_FADEUP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The datasets generated during the present study will not be publicly available, owing to the risk of disclosure or deduction of private individual information, but can be available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No