Effects of Exercise Training in Survivors of Lymphoma (LYMfit)

The LYMfit Study: Exercise Training to Prevent Cardiovascular Disease in Lymphoma Survivors

This study aims to compare the effects of aerobic exercise with or without addition of resistance exercise to usual care in individuals treated with anthracyclines for lymphomas and to compare exercise effects to age- and sex-matched individuals with no prior history of malignant diseases.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Lymphoma; Cardiotoxicity; Chemotherapeutic Toxicity; Physical Exercise
• Intervention / Treatment: Behavioral: Aerobic Exercise; Behavioral: Combined Aerobic and Resistance Exercise

Detailed Description

In this study, a comparison of the exercise effects between individuals previously treated for specific lymphoma diagnoses and individuals with no history of cancer will be conducted. Therefore, in addition to a randomized controlled trial in individuals with a previous lymphoma diagnosis (i.e., exercise groups and a non-exercising control group), a reference group comprising age- and sex-matched individuals with no history of a cancer diagnosis will also be included. Participants in the reference group will undergo the same exercise intervention as the aerobic exercise group. This study recruits through invitation only.

The primary endpoint in this study is the change in cardiorespiratory fitness, assessed as VO2peak. Secondary endpoints include common risk factors for cardiovascular disease and cardiometabolic health, other variables derived from the cardiopulmonary exercise test and lung function assessments, and muscle cellular endpoints from muscle biopsies obtained from m. vastus lateralis, in addition to patient-reported outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tormod S. Nilsen, PhD; Phone Number: 0047 95069857; Email: tormodsn@nih.no
• Study Contact Backup: Name: Helena Igelström, PhD; Phone Number: 0046 729999599; Email: helena.igelstrom@neuro.uu.se

Study Locations

• Norway
  • Oslo, Norway
    • Not yet recruiting
    • Norweigan School of Sport Sciences
    • Contact: Tormod S. Nilsen, PhD
• Sweden
  • Uppsala, Sweden
    • Recruiting
    • Helena Igelström
    • Contact: Helena Igelström, PhD
    • Contact: Anna Henriksson, PhD; Phone Number: 0046 709394175; Email: anna.km.henriksson@uu.se
    • Principal Investigator: Helena Igelström, PhD
    • Sub-Investigator: Anna Henriksson, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria Lymphoma participants:

• Listed in relevant registers
• Confirmed lymphoma diagnosis (i.e., Hodgkin lymphoma and aggressive non-Hodgkin lymphoma)
• Completed treatment in the past two to five years without relapse or second cancer
• Previous anthracycline treatment with or without mediastinal radiation
• No severe cancer-related fatigue (per self-report)

Inclusion Criteria Lymphoma participants and non-cancer reference group:

• Currently not performing >75 minutes/week of aerobic exercise
• Willing and able to adhere to all study procedures.

Exclusion Criteria Lymphoma participants:

• Relapse since diagnosis
• A history, or current presence, of another diagnosis of invasive cancer of any kind

Exclusion Criteria Lymphoma participants and non-cancer reference group:

• Presence of any uncontrolled- or recent cardiovascular disease
• Has undergone heart surgery
• Uses a pacemaker
• Pregnancy
• Unable to read and understand Swedish (applicable for the Swedish site only)
• Unable to read and understand Norwegian (applicable for the Norwegian site)
• Any physical or mental health condition restricting adherence to study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise; Aerobic Exercise twice weekly for 5 months.	Behavioral: Aerobic Exercise; Participants receive twice weekly supervised aerobic treadmill-based exercise sessions for five months. Session duration varies from 20 to 60 minutes, including warm-up, with exercise intensity ranging from 60 to 95% of peak heart rate. Maximal exercise capacity (VO2peak and peak heart rate) will be determined by the CPET performed by certified exercise physiologists at baseline.The exercise prescription will be sequenced so that the exercise intensity and -duration of each exercise varies within each week, leading to an accumulative increase in weekly exercise volume throughout the intervention. This intervention is also given to the Active Comparator group (i.e. non-cancer reference group)
Experimental: Combined Aerobic and Resistance Exercise; Combined Aerobic and Resistance Exercise twice weekly for 5 months.	Behavioral: Combined Aerobic and Resistance Exercise; Twice weekly, supervised combined aerobic and resistance exercise sessions will be offered to participants. Participants randomized to the combined aerobic and resistance training group will follow the same aerobic exercise prescription as described for the Aerobic Exercise arm. In addition, participants in this group will perform five resistance exercises after the aerobic sessions. The resistance exercises will be leg press, knee extension, and calf rise, followed by seated row and chest press. Following familiarization, the training load will progressively increase following a linear periodization model throughout the intervention. exercise prescription will be sequenced so that the exercise intensity and -duration of each exercise varies within each week, leading to an accumulative increase in weekly exercise volume throughout the intervention. Only Lymphoma participants can be randomized to this arm.
No Intervention: Standard Care; Standard Care, i.e no exercise intervention.
Active Comparator: Reference Aerobic Exercise; Aerobic Exercise twice weekly for 5 months.	Behavioral: Aerobic Exercise; Participants receive twice weekly supervised aerobic treadmill-based exercise sessions for five months. Session duration varies from 20 to 60 minutes, including warm-up, with exercise intensity ranging from 60 to 95% of peak heart rate. Maximal exercise capacity (VO2peak and peak heart rate) will be determined by the CPET performed by certified exercise physiologists at baseline.The exercise prescription will be sequenced so that the exercise intensity and -duration of each exercise varies within each week, leading to an accumulative increase in weekly exercise volume throughout the intervention. This intervention is also given to the Active Comparator group (i.e. non-cancer reference group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2peak	Peak oxygen uptake during a treadmill-based cardiopulmonary exercise test	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic- and diastolic heart chamber dimensions	Cardiac morphology and function will be assessed by echocardiography (2D and 3D echocardiography and 2D strain echocardiography)	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Systolic- and diastolic longitudinal strain	Cardiac morphology and function will be assessed by echocardiography (2D and 3D echocardiography and 2D strain echocardiography)	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Lean body mass	Body composition will be assessed by dual x-ray absorptiometry	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Fat mass	Body composition will be assessed by dual x-ray absorptiometry	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Forced Vital Capacity	Lung function are assessed with spirometry.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Forced Expiratory Volume 1 sec	Lung function are assessed with spirometry.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Maximal voluntary ventilation	Lung function are assessed with spirometry.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Diffusion capacity	Diffusion capacity for carbon monoxide is assessed with single breath diffusion capacity test.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Physical activity	Actigraph accelerometer with physical activity diary. 7 days consecutive measurement at each timepoints.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Physical activity	Patient reported physical activity is assessed with Godin Leisure-Time Exercise Questionnaire	Baseline, 10-12 weeks from baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Global Health related Quality of life	Patient reported health related quality of life will be assessed with EORTC QLQ C 30	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Blood volume	Will be assessed in Norway only. Using the carbon monoxide rebreathing method.	Baseline, five months from baseline (i.e. end of intervention) and 2 years from baseline
Muscle fiber area	Will be assessed in Norway only. Change in muscle morphology will be assessed in muscle biopsies using immunohistochemistry	Baseline, five months from baseline (i.e. end of intervention)
Muscle fiber type	Will be assessed in Norway only. Change in muscle morphology will be assessed in muscle biopsies using immunohistochemistry	Baseline, five months from baseline (i.e. end of intervention)
Muscle mitochondria mass	Will be assessed in Norway only. Change in mitochondrial proteins will be assessed in muscle biopsies using western blot	Baseline, five months from baseline (i.e. end of intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle genome-wide DNA methylation and gene expression	Will be assessed in Norway only. For a sub-group of participants, muscle biopsies will be further processed for RNA and DNA	Baseline, five months from baseline (i.e. end of intervention)
Adverse events	Medical records and Patient reported outcome version of the Common Terminology Criteria for Adverse Events.	Five months from baseline (i.e. end of intervention)

Collaborators and Investigators

• Sponsor: Norwegian School of Sport Sciences
• Collaborators: Uppsala University
• Investigators: Principal Investigator: Tormod S. Nilsen, PhD, Norwegian School of Sport Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Lymphoma; Cardiovascular Diseases; Cardiotoxicity
• Other Study ID Numbers: LYMfit

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