The Munich Adrenaline Cancer Study

Study Overview
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Brief Summary
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Observational studies report associations between physical activity and survival in some types of adult cancer. In addition, some exercise-induced molecules such as catecholamines (e.g., adrenaline) are known to change cancer cell signalling, proliferation and have been linked to clinical outcomes such as survival. The aim of this study is to analyse changes in adrenaline concentration with a single high-intensity interval exercise intervention on a cycle ergometer in children and adolescents during treatment for cancer and to examine the feasibility of the study concept.

Detailed Description
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Exercise is generally recommended as an adjunct therapy for adult cancer patients as it counteracts the adverse effects of cancer and its treatment. According to epidemiological data, exercise is also associated with a reduced risk of tumour developement and an improval of survival in some tumours. However, the underlying mechanisms by which exercise affects tumour cells are poorly understood in adult cancer patients and mostly unknown in children. Recent studies demonstrate anti-cancer effects of exercise-induced adrenaline through natural killer cell mobilisation and Hippo signalling. In addition, several exercise-induced molecules such as catecholamines (e.g., adrenaline) are known to change cancer cell signalling, proliferation and have been linked to clinical outcomes such as survival. The aim of this pilot study is the analysation of exercise-induced changes in adrenaline concentration in childhood cancer patients and to show feasibility of the study concept. Following recruitment within the first and third cycle of chemotherapy and consent for study participation, all recruited patients perform a single high-intensity interval exercise intervention on a cycle ergometer. Intensity of the intervals is examined both subjectively via a scale for rate of perceived exertion and objectively via changes in lactate concentration pre- and post-exercise as well as heart rate monitoring. Blood samples are taken by trained personnel staff and prepared for processing (centrifuged, snap-frozen). Changes in adrenaline concentration are measured with a commercial ELISA kit. For further identification of metabolites that change with exercise, a non-biased mass spectrometry metabolomics analysis will be used.

Official Title
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Changes in Metabolite Concentrations After a Single High-intensity Interval Exercise Intervention During Treatment for Childhood Cancer - A Pilot Study

Conditions
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Childhood Cancer

Intervention / Treatment
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* Other: Single high-intensity interval exercise intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed pediatric cancer or relapse aged 6-18 years between the first and third cycle of chemotherapy diagnosis and treatment at the Kinderklinik München Schwabing, Department of Paediatrics and Children's Cancer Research Centre, Technical University of Munich German language informed consent as documented by signature Exclusion Criteria: Any medical contraindication with respect to a high-intensity interval exercise intervention (e.g., cardiovascular complications, comorbidities, bleeding risk, pain, infection, nausea, orthopedic impairment of the lower extremities) inability to follow the procedures and understand the intervention and assessment of the study, e.g., due to cognitive impairment, language problems, psychological disorders etc.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-intensity interval exercise intervention<br>Change according to definition. | Other: Single high-intensity interval exercise intervention<br>* Study participants perform a single bout of exercise on a cycle ergometer (high-intensity interval exercise intervention) within the first and third cycle of chemotherapy. Following a 2 minute warm-up, the interval protocol comprises 10 intervals à 15 seconds with high intensity and 60 seconds low intensity in-between. Blood samples are taken at t0 pre-exercise (after a 10 minute rest) and at t1 immediately post-exercise via central catheter (Hickman/port).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in adrenaline concentration | Blood samples are collected at rest pre-exercise (t0) and post-exercise (t1) via a central catheter and prepared for processing by trained personnel (centrifuged, snap-frozen). Both at t0 and t1, 4,9ml blood are taken for adrenaline and lactate concentration (see secondary outcomes). Serum adrenaline concentration is measured with an ELISA kit in mmol/l. | Pre-exercise (at rest, t0) and post-exercise (within 3 min, t1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the study concept | Feasibility of the study concept is examined via compliance, acceptance and safety. Detailed documentation ensures completeness of feasibility aspects. | Through study completion, on average 14 days | 
| Lactate concentration | Lactate concentration is analysed to examine the level of intensity of the single high-intensity interval exercise intervention. Blood samples are collected at rest pre-exercise (t0) and post-exercise (t1), both 4,9ml, via a central catheter and prepared for processing by trained personnel. Lactate concentration is measured with Biosen C-Line in mmol/l. | Pre-exercise (at rest, t0) and post-exercise (within 3 min, t1) | 
| Heart rate | Heart rate monitoring is used to objectively measure the level of intensity during the single high-intensity interval exercise intervention for safety monitoring. Heart rate levels are documented at rest pre-exercise, after every interval and post-exercise. | Pre-exercise (at rest, t0), during high-intensity interval exercise intervention and post-exercise (within 3 min, t1) | 
| Physical activity before diagnosis | Physical activity levels are investigated using a standardised questionnaire (ActiOn) to evaluate the extent, range and intensity of physical activity shortly before the diagnosis. This questionnaire was developed for children and adolescents during and after treatment for childhood cancer. | Once, pre-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, metabolomics, high-intensity interval exercise intervention