SURfit - A Physical Activity Intervention for Childhood Cancer Survivors

Study Overview
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Brief Summary
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Exercise can play a major role to mitigate or even prevent late effects in cancer survivors, such as cardiovascular disease, obesity, osteoporosis, fatigue, depression, reduced quality of life, mental health and physical performance. The objective of this study is to assess the effect of an exercise program of 1 year on cardiovascular health, obesity and diabetes, osteoporosis, physical fitness, mental health and quality of life in childhood cancer survivors. The investigators will recruit childhood cancer survivors aged 16 years and above from three Swiss paediatric oncology clinics and randomize them into an intervention and a control group. The intervention group will be asked to increase physical activity for 1 year by at least 2.5 hours of intense physical activity weekly. Regular feedback will be given via a step counter, an online activity diary, and by the centre staff. The control group participants will keep their activity level constant. All participants will be seen after 3, 6 and 12 months to assess health and quality of life parameters over one year. After 1 year, the control group is offered to receive the same intervention to profit as well from an active lifestyle. If the program shows to be effective, a complete package will become available to interested centres treating paediatric cancer patients in Switzerland to promote exercise in all survivors. The program will allow clinicians without previous experience in exercise counselling to improve the care of their patients.

Official Title
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Effects of a 1-year Partially Supervised Exercise Program in Childhood Cancer Survivors - a Randomized Controlled Trial

Conditions
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Late-effects of Childhood Cancer

Intervention / Treatment
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* Behavioral: partially supervised exercise intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Registered in the Swiss Childhood Cancer Registry. Age at cancer diagnosis <16 years. Diagnosed with a cancer classifiable within the International Classification of Childhood Cancer (ICCC-3) or diagnosed with a Langerhans Cell Histiocytosis. Diagnosed and/or treated at the University Children's Hospital Basel, Cantonal Hospital of Aarau and/or Cantonal Hospital of Lucerne. Survived ≥5 years since primary cancer diagnosis or any subsequent cancer event (relapse or further cancer diagnoses) Age at the time of the study ≥16 years Informed Consent as documented by signature Exclusion Criteria: Participation in another clinical trial <4 weeks prior to baseline assessment (eventually later re-enrolment) Contradiction to one of the inclusion criteria mentioned above Inability to exercise Exercise potentially harmful Women who are pregnant or breast feeding Women who intend to become pregnant during the course of the study Instable clinical condition (eventually later re-enrolment) Under treatment for relapse or further cancer diagnoses Cardiac arrhythmias under exercise (during baseline assessment or by history) Diagnosis of diabetes <3 months ago (eventually re-enrolment after 3 months if diabetes is under good control) Detection of a clinical condition that needs immediate treatment during baseline assessments (eventually re-enrolment after 3 months if in stable clinical condition) Planned relevant surgeries for the next 12 months Major musculoskeletal injuries, fractures <2 months ago (eventually later re-enrolment) Recent change in medication that interfere with the parameters of the CVD risk score (primary outcome) <1 month ago (eventually later re-enrolment) >4 hours of reported vigorous activities per week Inability to follow the procedures and understand the intervention and assessments of the study e.g. due to cognitive impairment, language problems, psychological disorders etc.

Ages Eligible for Study
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Minimum Age: 16 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Partially supervised exercise intervention: Survivors in the intervention group will be asked to add at least 2.5 hours of intense physical activities per week. These should include at least 30 min of strength building exercises and 2 hours of aerobic exercises per week. Exercise bouts lasting 20 min or longer will be counted with respect to total weekly training time. | Behavioral: partially supervised exercise intervention<br> <br> * Other names: physical activity intervention;|
| No Intervention: Control Group<br>The control group will keep their physical activity level constant over the 1 year of the study. Thereafter, they will have the opportunity to receive the same intervention than the intervention group had received (off-trial) to benefit in the same way from an active lifestyle. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite cardiovascular risk score [z-score] | summarized mean z-score of waist circumference, blood pressure, HOMA-IR, inverted high density lipoprotein cholesterol, triglycerides and cardiorespiratory fitness | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist circumference [cm] |  | 3, 6, and 12 months | 
| Systolic and diastolic blood pressure [mmHg] |  | 3, 6, and 12 months | 
| Homeostasis Model Assessment Insulin Resistance (HOMA-IR) | calculated from insulin and glucose | 6 and 12 months | 
| HbA1C [mmol/mol] |  | 6 and 12 months | 
| Insulin resistance from response to oral glucose tolerance test (oGTT) | Assessment of fasting glucose [mmol/l] and insulin [mIU/l] and glucose 2 hours after drinking of a glucose solution | 12 months | 
| Inverted high-density lipoprotein cholesterol (HDL) [mmol/l] |  | 6 and 12 months | 
| Low-density lipoprotein cholesterol (LDL) [mmol/l] |  | 6 and 12 months | 
| Total cholesterol [mmol/l] |  | 6 and 12 months | 
| Triglycerides [mmol/l] |  | 6 and 12 months | 
| Body Mass Index (BMI) [z-score] | Calculated from height and weight | 3, 6, and 12 months | 
| Absolute [kg] and relative [%] body fat mass | Assessed with two methods: skinfold measurement (3, 6, and 12 months) and dual x-ray absorptiometry (DXA, 12 months only). | 3, 6, and 12 months | 
| Areal bone mineral density [g/cm2 and z-scores] | Bone mineral density for total body, lumbar spine, and femoral neck assessed with dual x-ray absorptiometry (DXA) | 12 months | 
| Bone mineral content [g/cm and z-scores] | Bone mineral content for total body, lumbar spine, and femoral neck assessed with dual x-ray absorptiometry (DXA) | 12 months | 
| Total cross sectional bone area [mm2 and z-scores] | Cross sectional area of the distal and proximal sites of radius and tibia assessed with peripheral quantitative computer tomography (pQCT) | 12 months | 
| Cortical cross sectional bone area [mm2 and z-scores] | Cross sectional area of the proximal site of radius and tibia assessed with peripheral quantitative computer tomography (pQCT) | 12 months | 
| Total and trabecular bone mineral density [g/cm3 and z-scores] | Bone mineral density of the distal site of radius and tibia assessed with peripheral quantitative computer tomography (pQCT) | 12 months | 
| Cortical bone mineral density [g/cm3 and z-scores] | Bone mineral density of the proximal site of radius and tibia assessed with peripheral quantitative computer tomography (pQCT) | 12 months | 
| Muscle cross-sectional area [cm2 and z-scores] | Muscle cross-sectional area of the proximal site of radius and tibia assessed with peripheral quantitative computer tomography (pQCT) | 12 months | 
| Peak oxygen uptake (VO2max) [ml/(kg*min) and % predicted] | Assessed with maximal spiroergometry test | 6 and 12 months | 
| Peak performance [watt/kg and % predicted] | Assessed with maximal spiroergometry test | 6 and 12 months | 
| Heart rate recovery [delta beats/min] | Assessed at the end of the maximal spiroergometry test: delta beats/min between peak heart rate and heart rate 1 minute post exercise. | 6 and 12 months | 
| Hand grip strength in the left and right hand [kg] | Assessed with a hydrolic hand grip dynamometer. | 6 and 12 months | 
| Leg strength and endurance [repetitions/min] | Assessed with the 1 minute sit-to-stand test | 6 and 12 months | 
| Total physical activity [counts/min] | Assessed by accelerometer | 6 and 12 months | 
| Moderate to vigorous physical activities [minutes/day] | Assessed by accelerometer | 6 and 12 months | 
| High impact activities with ground forces >3.9 G [n/day] | Assessed by accelerometer | 6 and 12 month | 
| Sedentary behaviour [minutes/day] | Assessed by accelerometer | 6 and 12 months | 
| Number of steps per day [steps/day] | Assessed by accelerometer | 6 and 12 months | 
| Health related quality of life [T-score with mean=50, standard deviation=10 and range=0-100] | Health related quality of life assessed by the self-reported questionnaire short form 36 (SF-36). | 6 and 12 months | 
| Psychological distress [T-score with mean=50, standard deviation=10 and range=0-100] | Psychological distress assessed by the self-reported questionnaire Brief Symptom Inventory (BSI). | 6 and 12 months | 
| Fatigue on a visual analogue scale (VAS) [mm] |  | 3, 6 and 12 months | 
| Fatigue | Fatigue assessed with the self-reported questionnaire Checklist of Individual Strength (CIS). | 3, 6 and 12 months | 
| Number of adverse events and serious adverse events [n] | Number of participants with adverse events and exercise related complications categorized into seriousness of the event (adverse event [AE] or severe adverse event [SAE]). | 3, 6 and 12 months | 
| Proportion of aimed physical activity reached [%] | Only intervention participants: compliance with intervention | 12 months | 
| Number of weeks where physical activity aim was reached [n/year] | Only intervention participants: compliance with intervention | 12 months | 
| Number of missing days in the online diary [n/year] | Only intervention participants: compliance with intervention | 12 months |