Clinical trial NCT05063760: Exercise in Testicular Germ Cell Cancer Survivors
Official title: Exercise in Prevention & Treatment of Chemotherapy-related Late Toxicity in Testicular Germ Cell Cancer Survivors: the Role of Skeletal Muscle
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Testicular Germ Cell Tumor
Keywords: TGCT
exercise intervention
Magnetic resonance spectroscopy
skeletal muscle
chemotherapy-induced metabolic toxicity
Lead sponsor: Slovak Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Comenius University
First posted: 2021-10-01
Enrollment: 60
Sex: MALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: controled trial with exercise intervention
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: change in the glucose tolerance
timeFrame: parameter will be measured before and after 6 month intervention
measure: change in resting energy expenditiure and metabolic substrate preference
timeFrame: parameters will be measured twice before and after 6 month intervention
measure: change anthropometric parameters of obesity
timeFrame: parameters will be measured twice before and after 6 month intervention
measure: change physical fitness
timeFrame: parameter will be measured twice before and after 6 month intervention
Secondary outcomes:
measure: change in quality of life for cancer patients
timeFrame: measured twice before and after 6 month intervention
measure: change in muscle strength
timeFrame: measured twice before and after 6 month intervention
measure: change in cognitive functions
timeFrame: measured twice before and after 6 month intervention
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: National Cancer Institute
state: Please Select
city: Bratislava
country: Slovakia
facility: Biomedical Research Center Slovak Academy of Sciences
state: Please Select
Study officials:
affiliation: Biomedical Research Center, Slovak Acad Sci
name: Barbara Ukropcova, MD, PhD, Prof
role: PRINCIPAL_INVESTIGATOR
References: