Exercise in Testicular Germ Cell Cancer Survivors (ExCell)

Exercise in Prevention & Treatment of Chemotherapy-related Late Toxicity in Testicular Germ Cell Cancer Survivors: the Role of Skeletal Muscle

Regular exercise is effective in prevention & treatment of chronic diseases. Exercise can reduce late toxicity of chemotherapy, commonly found in cancer survivors, which is yet to be translated into clinical practice.

Mechanisms of exercise benefits in oncologic patients are far from being elucidated, and include increase in muscle mass, reduction of fat mass, systemic inflammation and cardiometabolic risk. Synchronization of exercise adaptive response is, to an extent, mediated by bioactive molecules released from muscle, with anti-inflammatory & tumor-suppressing properties. Muscle satellite cells are a source of regeneration, muscle structural integrity & functional capacity. Phenotypes of muscle cells, such as secretory profile, lipid & glucose metabolism, mirror clinical phenotypes of the donor. Importantly, muscle cells' metabolism in vitro can be modulated by 8-12 week training in vivo. Epigenetic mechanisms regulating muscle & systemic metabolism in cancer survivors are not yet understood.

Study Overview

• Status: Active, not recruiting
• Conditions: Testicular Germ Cell Tumor
• Intervention / Treatment: Behavioral: aerobic-strength exercise intervention (6-months)

Detailed Description

Aims:

• To assess the impact of 6-month supervised, individualized aerobic-strength exercise training intervention in cancer survivors with chemotherapy-induced late toxicity . (i) on the whole-body energy and glucose metabolism, anthropometric parameters, physical fitness & activity profile, motor functions and quality of life in testicular germ cell cancer (TGCC) survivors, more than 3 years after cisplatin-based chemotherapy; with the 2-year follow up; . (ii) on skeletal muscle mass, morphology as well as functional and metabolic state detected in vivo (31P-MR spectroscopy).

(iii) on metabolic characteristics of primary skeletal muscle cells;

• To determine the impact of exercise intervention on circulating bioactive molecules (exerkines), putative mediators of exercise health benefits as well as on levels of circulating inflammatory cytokines, which likely contribute to the pathogenesis of chemotherapy-induced late toxicity;
• To evaluate the role of (a) selected exercise-regulated bioactive molecules, (b) exercise-mimicking treatment (by electric pulse stimulation) and (c) cisplatin treatment on metabolism and mitochondrial function of differentiated human muscle cells in culture;
• To investigate the associations between intervention-induced shifts in circulating bioactive molecules and selected metabolic, anthropometric and motor parameters.

The generated results will enable us (i) to gain a better insight into pathomechanisms of muscle-associated chemotherapy-induced late toxicity and the role of skeletal muscle & systemic mediators in the exercise-induced health benefits in TGCC survivors; and (ii) to validate the effectiveness of the individually-tailored exercise intervention in reducing chemotherapy-related toxicity in patients with TGCC, with the aim to transfer this knowledge into clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Slovakia
  • Please Select
    • Bratislava, Please Select, Slovakia, 800 00
      • National Cancer Institute
    • Bratislava, Please Select, Slovakia, 84505
      • Biomedical Research Center Slovak Academy of Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• TGCT survivors, with chemotherapy-induced metabolic toxicity, men, 25-55 years old, with the capacity to undergo training, signed written informed consent

Exclusion Criteria:

• serious / uncontrolled chronic diseases, non-compliance, other health issues as assessed by oncologists / investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TGCT patients - exercise; TGCT survivors, men, 25-55 yrs old, 3 and more years after successful treatment of TGCT, with the capacity to undergo aerobic-strength intervention assessed by cardiologist	Behavioral: aerobic-strength exercise intervention (6-months); 6 month supervised exercise intervention in TGCT survivors (1 hour sessions 3 x per week),
No Intervention: TGCT patients - nonexercising controls; TGCT survivors, men, 25-55 yrs old, 3 and more years after successful treatment of TGCT, with the capacity to undergo aerobic-strength intervention assessed by cardiologist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the glucose tolerance	change in glucose tolerance (as measured by oral glucose tolerance test)	parameter will be measured before and after 6 month intervention
change in resting energy expenditiure and metabolic substrate preference	change in resting energy expenditure calculated by Weir equation from VO2 and metabolic substrate preference RQ VCO2/VO2 (as measured by indirect calorimetry)	parameters will be measured twice before and after 6 month intervention
change anthropometric parameters of obesity	BMI (kg.m-2) , fat mass (% electric bioimpedance), lean body mass (% electric bioimpedance), visceral adiposity (%, elecgtric bioimpedance)	parameters will be measured twice before and after 6 month intervention
change physical fitness	VO2max (mlO2 per kg BW min) as measured by bicycle spiroergometry	parameter will be measured twice before and after 6 month intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in quality of life for cancer patients	validated questionnaire	measured twice before and after 6 month intervention
change in muscle strength	dynamometry	measured twice before and after 6 month intervention
change in cognitive functions	standardised cognitive test Cogstate	measured twice before and after 6 month intervention

Collaborators and Investigators

• Sponsor: Slovak Academy of Sciences
• Collaborators: Comenius University
• Investigators: Principal Investigator: Barbara Ukropcova, MD, PhD, Prof, Biomedical Research Center, Slovak Acad Sci

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): December 1, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic resonance spectroscopy; exercise intervention; skeletal muscle; TGCT; chemotherapy-induced metabolic toxicity
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms
• Other Study ID Numbers: 2/0164/20; SRDA19-0411 (Other Grant/Funding Number: Slovak Research and Development Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: we will share IPD upon 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