Exercise in Adolescents With Cancer (EXERCADOL)

Exercise Intervention for Adolescents With Cancer (EXERCADOL): A Randomized Controlled Trial

The investigators will study the effects of an supevised exercise intervention along the duration of intensive treatment (neoadjuvant [solid tumours]/intense chemotherapy [leukemias], expected median duration 5-6 months) on several health-related variables. Participants will be recruited from 4 hospitals in Madrid (Spain). Inclusion criteria: male/female aged 12-19 years, newly diagnosed--or relapse of-- a malignant extracranial tumour; not having received any type of therapy--except surgery--at the time of diagnosis; adequate health status (Karnofsky/Eastern Cooperative Oncology Group scale score ≥50/≤2); to understand Spanish language and to provide written informed consent. The investigators will recruit ≥136 participants and conduct a randomised controlled trial. The intervention group will follow a supervised concurrent exercise program from the start to the end of intensive treatment. The exercise intervention will be performed in the hospital gymnasium or in the patients' ward (during neutropenic phases), and will also include supervised online sessions. Additionally, the intervention group will perform include inspiratory muscle training. The following outcomes will be assessed at baseline (diagnosis), end of treatment, and at 3-month follow-up in all participants: echocardiography-determined left ventricular function (primary outcome); and other echocardiography-determined variables, cardiac biomarkers, blood pressure, blood lipids, body composition, physical activity levels, energy intake, cardiorespiratory fitness, muscle strength, functional mobility, health-related quality of life, cancer-related fatigue, clinical variables, and potential biological underpinnings of exercise multisystemic benefits (metabolic and inflammatory markers, plasma proteome, gut microbiome, and immune function).

Study Overview

• Status: Recruiting
• Conditions: Adolescent Cancer
• Intervention / Treatment: Behavioral: Physical exercise

Detailed Description

Background. Health promotion interventions are needed during adolescent cancer treatment to facilitate the acquisition of good health practices as patients transition to survivorship. Although meta-analytical evidence supports the health benefits of exercise in the context of childhood cancer, there is scant data focusing solely on adolescents.

Hypothesis and objectives. The investigators hypothesise that a supervised exercise intervention combined with lifestyle counselling during treatment for adolescent cancer will provide several health benefits, particularly related to the cardiometabolic profile. Thus, the investigators will study the effects of a supervised exercise intervention along the duration of intensive treatment (neoadjuvant [solid tumours]/intense chemotherapy [leukaemias], expected median duration 5-6 months) on several health-related variables.

Setting and Methods. Participants will be recruited from 4 hospitals in Madrid (Spain). Inclusion criteria: male/female aged 12-19 years, newly diagnosed with (or having relapse of) a malignant extracranial tumour; not having received any type of therapy--except surgery--at the time of diagnosis; adequate health status (Karnofsky/Eastern Cooperative Oncology Group scale score ≥50/≤2); to understand Spanish language and to provide written informed consent. The investigators will recruit ≥136 participants and conduct a randomised controlled trial (1:1 ratio randomisation with a block on gender and tumour type [leukaemias/lymphomas]). In addition to usual care, the two groups will receive health counselling twice a month (i.e., psychological intervention based on motivational interviewing techniques, as well as guidance on heathy activity, sleeping, and dietary habits). The intervention group will follow a physical exercise and lifestyle counselling program. The exercise intervention will be performed in the hospital gymnasium (3 sessions/week of aerobic and resistance exercises), except for neutropenic phases--during which time sessions will be performed in the patients' ward--and will also include online sessions. Inspiratory muscle training (5 days/week) will be also performed. Patients in the control group will have the option to go to the hospital gymnasium twice a month (to perform playing activities) in order to maximize compliance to the study and to maintain contact with them. The following outcomes will be assessed at baseline (diagnosis), end of treatment, and at 3-month follow-up in all participants: echocardiography-determined left ventricular function (primary outcome); and other echocardiographic variables, cardiometabolic biomarkers, blood pressure, blood lipids, dual-energy X-ray absorptiometry-determined body composition (fat [including visceral adipose tissue]/lean mass, bone mineral content/density), energy intake, cardiorespiratory fitness, muscle strength, functional mobility, health-related quality of life, cancer-related fatigue, clinical variables (survival, treatment tolerability, hospitalisation length), and potential biological underpinnings of exercise multisystemic benefits (cardiometabolic and inflammatory biomarkers, gut microbiome, and immune function [lymphocyte subpopulations, natural killer cell cytotoxicity]) (secondary outcomes).

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alejandro Lucia; Phone Number: +34661393101; Email: alejandro.lucia@universidadeuropea.es

Study Locations

• Spain
  • Madrid, Spain
    • Recruiting
    • UEM
  • Spain
    • Villaviciosa de Odón, Spain, Spain, 28670
      • Recruiting
      • Universidad Europea de Madrid
      • Contact: Phone Number: +34661393101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed with a malignant extracranial tumour
• Not having received any therapy--except surgery--at diagnosis
• Adequate health status (Karnofsky/Eastern Cooperative Oncology Group scale score ≥50/2)
• To understand Spanish language and provide written informed consent.

Exclusion Criteria:

• Life expectancy <3 months
• Comorbidity/acute condition contraindicating exercise practice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard care
Experimental: Intervention; The intervention group will follow a supervised physical exercise program.	Behavioral: Physical exercise; the intervention group will follow a supervised physical exercise intervention--see below. The exercise program (3 supervised sessions/week of aerobic and muscle strength exercises) will be performed: (a) in the hospital gymnasium, or (b) in the patients' room (during phases of treatment-induced immunodepression, where isolation is needed to prevent infections), or (c) online (for those unable to attend the hospital on that day/s). It will also include specific training of the respiratory ('inspiratory') muscles (e.g., diaphragm) on 5 days/week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left-ventricular (LV) function (LV ejection fraction) from baseline to end of treatment	Echocardiography-determined LV ejection fraction (unit = %)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in left-ventricular (LV) function (LV fractional shortening) from baseline to end of treatment	Echocardiography-determined LV fractional shortening (unit = %)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in global longitudinal strain (GLS) of the left ventricle from baseline to end of treatment	Echocardiography-determined GLS (%)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left-ventricular (LV) function (LV ejection fraction) from baseline to follow-up	Echocardiography-determined LV ejection fraction (unit = %)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in left-ventricular (LV) function (LV fractional shortening) from baseline to follow-up	Echocardiography-determined LV fractional shortening (unit = %)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
Change in serum lipid profile (cholesterol) from baseline to end of treatment	Total/HDL/LDL-cholesterol will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
Change in serum lipid profile (cholesterol) from baseline to follow-up	Total/HDL/LDL-cholesterol will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
Change in serum lipid profile (triglycerides) from baseline to end of treatment	Tiglycerides will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
Change in serum lipid profile (triglycerides) from baseline to follow-up	Tiglycerides will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
Change in adiposity index from baseline to end of treatment	Waist-to-hip ratio (no units)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in adiposity index from baseline to follow-up	Waist-to-hip ratio (no units)	Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow-up)
Change in DXA measures of lean mass from baseline to end of treatment	DXA-determined total lean mass (grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in DXA measures of fat mass from baseline to follow-up	DXA-determined total fat mass (grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in inspiratory muscle strength (PImax) from baseline to end of treatment	PImax (units = cmH20) will be determined using a mouth pressure meter with the best result from 3 attempts (interspersed with rest periods of ≥1 min-duration) taken.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in inspiratory muscle strength (PImax) from baseline to follow-up	PImax (units = cmH20) will be determined using a mouth pressure meter with the best result from 3 attempts (interspersed with rest periods of ≥1 min-duration) taken.	Assessed at three time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in clinical variables (days of hospitalization) from baseline to end of treatment	Total hospitalisation length (number of days)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
Change in metabolic markers (glucose) from baseline to end of treatment	Serum fasting glycaemia (mg/dL)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
Change in metabolic markers (glucose) from baseline to follow-up	Serum fasting glycaemia (mg/dL)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in metabolic markers (HOMA-IR) from baseline to end of treatment	Homeostasis model assessment-insulin resistance index (HOMA-IR) (molar units)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in metabolic markers (HOMA-IR) from baseline to follow-up	Homeostasis model assessment-insulin resistance index (HOMA-IR) (molar units)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in gut microbiome (alpha-diversity) from baseline to end of treatment	α-diversity	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in gut microbiome (alpha-diversity) from baseline to follow-up	α-diversity	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in gut microbiome (beta-diversity) from baseline to end of treatment	beta-diversity	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in gut microbiome (beta-diversity) from baseline to follow-up	Beta-diversity	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in gut microbiome (specific bacteria) from baseline to end of treatment	Changes in bacteria abundance	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in gut microbiome (specific bacteria) from baseline to follow-up	Changes in bacteria abundance	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in Immune phenotype (lymphocyte subpopulations) from baseline to end of treatment	Lymphocyte subpopulations (%)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
Change in Immune phenotype (lymphocyte subpopulations) from baseline to follow-up	Lymphocyte subpopulations (%)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in Immune phenotype (natural killer (NK) cells) from baseline to end of treatment	NK cell subsets (%)	Assessed at two time points: (1) at baseline (diagnosis); (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in Immune phenotype (NK cells) from baseline to follow-up	NK cell subsets (%)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in Immune function from baseline to end of treatment	NK cell receptors	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in immune function from baseline to follow-up	NK cell receptors	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in global longitudinal strain (GLS) of the left ventricle from baseline to 3 months after the end of treatment (follow-up)	Echocardiography-determined GLS (%)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in 'clinic' arterial blood pressure from baseline to end of treatment	Arterial blood pressure (BP) (units = mmHg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
Change in 'clinic' arterial blood pressure from baseline to follow-up	Arterial blood pressure (BP) (units = mmHg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in DXA measures of lean mass from baseline to follow-up	DXA-determined total lean mass (grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in muscle strength from baseline to follow-up	The 5-repetition maximum (commonly abbreviated as 5RM), which is the maximum strength capacity to perform 5 repetitions until momentary muscular exhaustion, will be measured for leg press and bench press, as well as for seatead lateral row, lateral pull down and knee extension (units = kg).	Assessed at two time points: (1) at baseline (diagnosis);and (2) 3 months after the end of treatment (follow-up)
Survival from baseline to follow-up	Number of days elapsed from diagnosis until the end of the study (or death, tumor recurrence, or transplant)	Assessed from baseline (diagnosis) until 3 months after end of treatment (follow-up)
Treatment tolerability from baseline to end of treatment	Number of days of treatment interruption/delay	Assessed from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in chronic systemic inflammation (high-sensitivity C-reactive protein) from baseline to end of treatment	High-sensitivity C-reactive protein (mg/L)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in chronic systemic inflammation (high-sensitivity C-reactive protein) from baseline to follow-up	High-sensitivity C-reactive protein (mg/L)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from baseline to end of treatment	NT-proBNP (units = pg/mL)	: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from baseline to 3 months after the end of treatment (follow-up)	NT-proBNP (units = pg/mL)	: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in cardiac troponin I from baseline to end of treatment	Cardiac troponin I (units = ng/mL)	: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in cardiac troponin I from baseline to 3 months after the end of treatment (follow-up)	Cardiac troponin I (units = ng/mL)	: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in left-ventricular (LV) mass from baseline to end of treatment	Echocardiography-determined LV mass (unit = grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in left-ventricular (LV) mass from baseline to follow-up	Echocardiography-determined LV mass (unit = grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) and (2) 3 months after the end of treatment (follow-up)
Change in relative wall thickness (RWT) from baseline to end of treatment	Echocardiography-determined RWT (units = cm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in relative wall thickness (RWT) from baseline to follow-up	Echocardiography-determined RWT (units = cm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in DXA measures of visceral adipose tissue (VAT) from baseline to end of tratment	DXA-determined VAT (unit = grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in DXA measures of visceral adipose tissue (VAT) from baseline to follow-up	DXA-determined VAT (grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in serum lipid profile (apolipoprotein B) from baseline to follow-up	Apolipoprotein B will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in serum lipid profile (apolipoprotein B) from baseline to end of treatment	Apolipoprotein B will be quantified with an automated chemistry analyser (units = mg/dL).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
Change in handgrip strength from baseline to end of treatment	Handgrip strength will be measured in both dominant and non-dominant arm (units = kg).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in handgrip strength from baseline to follow-up	Handgrip strength will be measured in both dominant and non-dominant arm (units = kg).	Assessed at two time points: (1) at baseline (diagnosis);and (2) 3 months after the end of treatment (follow-up)
Change in interventricular septum thickness (IVS) from baseline to end of treatment	Echocardiography-determined IVS (units = mm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in interventricular septum thickness (IVS) from baseline to 3 months after the end of treatment (follow-up)	Echocardiography-determined IVS (mm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in left-ventricular end-diastolic diameter (LVEDD) from baseline to end of treatment	Echocardiography-determined LVEDD (mL)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in left-ventricular LV end-diastolic diameter (LVEDD) from baseline to 3 months after the end of treatment (follow-up)	Echocardiography-determined LVEDD (mL)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in left-ventricular posterior wall thickness (LVPW) from baseline to end of treatment	Echocardiography-determined LVPW (mm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in left-ventricular posterior wall thickness (LVPW) from baseline to 3 months after the end of treatment (follow-up)	Echocardiography-determined LVPW (mm)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in functional mobility (Timed Up and Go (TUG)) test) from baseline to end of treatment	Performance in TUG test (seconds)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in functional mobility (Timed Up and Down Stairs (TUDS)) from baseline to end of treatment	Performance in TUDS test (units = seconds)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in functional mobility (Timed Up and Down Stairs (TUDS) test) from baseline 3 months after the end of treatment (follow-up)	Performance in TUDS test (seconds)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in functional mobility (30-second chair stand test) from baseline to end of treatment	Performance in 30-second chair stand test (unit = number of repetitions)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in functional mobility (in 30-second chair stand test) from baseline 3 months after the end of treatment (follow-up)	Performance in in 30-second chair stand test (units = number of repetitions)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in body mass index (BMI) from baseline to end of treatment	BMI (weight (kg)/height squared (m2))	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in body mass index (BMI) from baseline to follow-up	BMI (weight (kg)/height squared (m2))	Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow-up)
Change in DXA measures of fat mass from baseline to end of treatment	DXA-determined total fat mass (grams)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in DXA measure of bone mineral density of the total body (less head) from baseline to end of treatment	DXA-determined subtotal bone mineral density (unit = g/cm2)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in DXA measure of bone mineral density of the total body (less head) from baseline to follow-up	DXA-determined subtotal bone mineral density (unit = g/cm2)	Assessed at two time points: (1) at baseline (diagnosis); and 3 months after the end of treatment (follow-up)
Change in cardiorespiratory fitness (VO2peak) from baseline to end of treatment	VO2peak will be determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like bicycle- or arm-crank ergometer -for those participants missing a lower limb- test (units = mL/kg/min)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in cardiorespiratory fitness (VO2peak) from baseline to follow-up	VO2peak will be determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like bicycle- or arm-crank -for those participants missing a lower limb- ergometer test (units = mL/kg/min).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in muscle strength from baseline to end of treatment	The 5-repetition maximum (commonly abbreviated as 5RM), which is the maximum strength capacity to perform 5 repetitions until momentary muscular exhaustion, will be measured for leg press and bench press, as well as for seated lateral row, lateral pull down and knee extension (units = kg).	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in clinical variables (global score of Common Terminology Criteria for Adverse Events [CTCAE]) from baseline to end of treatment	Common Terminology Criteria for Adverse Events [CTCAE, global score, 1 (low toxicity) to 5 (highest)]	Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis.
Change in clinical variables (global score of Common Terminology Criteria for Adverse Events [CTCAE]) from baseline to follow-up	Common Terminology Criteria for Adverse Events [CTCAE, global score, 1 (low toxicity) to 5 (highest])	Assessed continuously (every day) from baseline (diagnosis) until 3 months after the end of treatment (follow-up)
Change in metabolic markers (insulin) from baseline to end of treatment	Serum fasting insulinaemia (pmol/L)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in metabolic markers (insulin) from baseline to follow-up	Serum fasting insulinaemia (pmol/L)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in functional mobility (Timed Up and Go (TUG)) test) from baseline 3 months after the end of treatment (follow-up)	Performance in TUG test (seconds)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in health-related quality of life (HRQoL) from baseline to end of treatment	Paediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module (Patient's version), designed to measure paediatric/adolescent cancer specific HRQoL (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in health-related quality of life (HRQoL) from baseline 3 months after the end of treatment (follow-up)	Paediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module (Patient's version), designed to measure paediatric/adolescent cancer specific HRQoL (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in fatigue from baseline to end of treatment	Cancer-related fatigue (Paediatric Quality of Life (PedsQL)) Multidimensional Fatigue Scale, Patient's version (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in fatigue from baseline 3 months after the end of treatment (follow-up)	Cancer-related fatigue (Paediatric Quality of Life (PedsQL)) Multidimensional Fatigue Scale, Patient's version (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in energy and nutrient intake from baseline to end of treatment	Energy (total kcal/day) and substrate (carbohydrate, fat, protein, all in grams) intake, as estimated using the Nutrimind software based on the participants' reported food consumption frequencies in questionnaires	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in energy and nutrient intake from baseline 3 months after the end of treatment (follow-up)	Energy (total kcal/day) and substrate (carbohydrate, fat, protein, all in grams) intake, as estimated using the Nutrimind software based on the participants' reported food consumption frequencies in questionnaires	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in DXA measure of bone mineral density of the femoral neck from baseline to end of treatment	DXA-determined bone mineral density of the femoral neck (unit = g/cm2)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment).
Change in DXA measure of bone mineral density of the femoral neck from baseline to follow-up	DXA-determined total bone mineral density of the femoral neck (unit = g/cm2)	Assessed at two time points: (1) at baseline (diagnosis); and 3 months after the end of treatment (follow-up)
Change in peak power output (also known was 'peak work capacity') from baseline to end of treatment	Peak power output will be determined using a ramp-like cycle- or crank-ergometer-for those participants missing a lower limb-test (units = watts/kg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in in peak power output (also known was 'peak work capacity') from baseline to follow-up	Peak power output will be determined using a ramp-like cycle- or crank-ergometer-for those participants missing a lower limb-test (units = watts/kg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in the power output eliciting the 'ventilatory threshold' from baseline to end of treatment	The ventilatory threshold will be visually determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like cycle- or crank-ergometer-for those participants missing a lower limb-test (units = watts/kg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)]
Change in the power output eliciting the 'ventilatory threshold' from baseline to follow-up	The ventilatory threshold will be visually determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like cycle- or crank-ergometer-for those participants missing a lower limb-test (units = watts/kg)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in health-related quality of life (HRQoL) from baseline to end of treatment	Paediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module (Parent's version), designed to measure paediatric/adolescent cancer specific HRQoL (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in health-related quality of life (HRQoL) from baseline 3 months after the end of treatment (follow-up)	Paediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module (Parent's version), designed to measure paediatric/adolescent cancer specific HRQoL (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in fatigue from baseline to end of treatment	Cancer-related fatigue (Paediatric Quality of Life (PedsQL)) Multidimensional Fatigue Scale, Parent's version (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in fatigue from baseline 3 months after the end of treatment (follow-up)	Cancer-related fatigue (Paediatric Quality of Life (PedsQL)) Multidimensional Fatigue Scale, Parents' version (0 to 100 scale, with higher scores indicating better HRQoL). Units = 0 to 100.	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the range of movement (ROM) of the ankle in the relaxed position from baseline to end of treatment	Ankle's ROM in the relaxed position will be assessed using a goniometer, except for those patients with an amputated ankle or a tumor next to the ankle (units = º)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the range of movement (ROM) of the ankle in the relaxed position from baseline to follow-up	Ankle's ROM in the relaxed position will be assessed using a goniometer, except for those patients with an amputated ankle or a tumor next to the ankle (units = º)	Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow- up)
Change in the range of movement (ROM) of the ankle at dorsiflexion from baseline to end of treatment	Ankle's ROM at dorsiflexion will be assessed using a goniometer, except for those patients with an amputated ankle or a tumor next to the ankle (units = º)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the range of movement (ROM) of the ankle at dorsiflexion from baseline to follow-up	Ankle's ROM at dorsiflexion will be assessed using a goniometer, except for those patients with an amputated ankle or a tumor next to the ankle (units = º)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Change in the physical activity levels from baseline to end of treatment	Physical activity levels will be measured with the 'Youth Activity Profile' (YAP) questionnaire	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the physical activity levels from baseline to follow-up	Physical activity levels will be measured with the 'Youth Activity Profile' (YAP) questionnaire	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment
Change in the physical activity levels from baseline to end of treatment	Physical activity levels will be measured with the 'Assessment of Physical Activity Levels' (APAL) questionnaire (units = score from 5 to 20)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the physical activity levels from baseline to follow-up	Physical activity levels will be measured with the 'Assessment of Physical Activity Levels' (APAL) questionnaire (units = score from 5 to 20)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment
Change in the number of viral/bacterial/fungal infections from baseline to end of treatment	The number of viral/bacterial/fungal infections will be retrieved from medical records	Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the number of viral/bacterial/fungal infections from baseline to follow-up	The number of viral/bacterial/fungal infections will be retrieved from medical records	Assessed continuously (every day) from baseline (diagnosis) until 3 months after the end of treatment
Change in metabolic markers (glycated hemoglobin) from baseline to end of treatment	Serum fasting glycated hemoglobin (mmol/mol)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in metabolic markers (glycated hemoglobin) from baseline to follow-up	Serum fasting glycated hemoglobin (mmol/mol)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment
Change in left-ventricular (LV) hypertrophy from baseline to end of treatment	Age-specific >95th percentile for LV mass	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in left-ventricular (LV) hypertrophy from baseline to follow-up	Age-specific >95th percentile for LV mass	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment
Change in VO2 at the ventilatory threshold from baseline to end of treatment	VO2 at the ventilatory threshold will be determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like bicycle- or arm-crank ergometer -for those participants missing a lower limb- test (units = mL/kg/min)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in VO2 at the ventilatory threshold from baseline to follow-up	VO2 at the ventilatory threshold will be determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like bicycle- or arm-crank ergometer -for those participants missing a lower limb- test (units = mL/kg/min)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment
Change in toxicity grade from baseline to end of treatment	Toxicity grade will be assessed using the formula from Langlais et al (2022), where using the 5 adverse events of higher grade, provides a score from 5 (more toxicity) to 0 (less toxicity)	Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in toxicity grade from baseline to follow-up	Toxicity grade will be assessed using the formula from Langlais et al (2022), where using the 5 adverse events of higher grade, provides a score from 5 (more toxicity) to 0 (less toxicity)	Assessed continuously (every day) from baseline (diagnosis) until 3 months after the end of treatment
Change in the duration of viral/bacterial/fungal infections from baseline to end of treatment	The duration of viral/bacterial/fungal infections will be retrieved from medical records	Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in the duration of viral/bacterial/fungal infections from baseline to follow-up	The duration of viral/bacterial/fungal infections will be retrieved from medical records	Assessed continuously (every day) from baseline (diagnosis) until 3 months after the end of treatment
Adherence to the exercise intervention from baseline to end of treatment	The number of attended exercise sessions	Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in plasma cardiovascular-related targeted proteome from baseline to end of treatment	Olink® cardiovascular II reagent kit, which measures 92 cardiovascular related human protein biomarkers simultaneously (units = Normalized Protein Expression (NPX) values, Olink's arbitrary unit presented in log2 scale)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
Change in plasma cardiovascular-related targeted proteome from baseline to follow-up	Olink® cardiovascular II reagent kit, which measures 92 cardiovascular related human protein biomarkers simultaneously (units = Normalized Protein Expression (NPX) values, Olink's arbitrary unit presented in log2 scale)	Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (i.e., follow-up)

Collaborators and Investigators

• Sponsor: Universidad Europea de Madrid

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: cancer; lifestyle; cardiac function
• Additional Relevant MeSH Terms: Neoplasms; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: Universidad Europea de Madrid

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As per Spanish regulations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No