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

Brief Summary

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).

Primary Outcomes

Secondary Outcomes

• Treatment tolerability from baseline to end of treatment(Assessed from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment))
• Change in clinical variables (days of hospitalization) from baseline to end of treatment(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(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(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(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(Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up))
• Change in chronic systemic inflammation (high-sensitivity C-reactive protein) from baseline to end of treatment(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(Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up))
• Change in plasma cardiometabolic-related targeted proteome from baseline to end of treatment(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 cardiometabolic-related targeted proteome from baseline to follow-up(Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (i.e., follow-up))
• Change in gut microbiome (alpha-diversity) from baseline to end of treatment(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(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(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(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(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(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(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(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(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(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(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(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(: 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)(: 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(: 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)(: 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(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(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(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(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(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(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(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(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(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(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(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)(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(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)(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(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)(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(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(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)(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(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)(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(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(Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow-up))
• Change in 'clinic' arterial blood pressure from baseline to end of treatment(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(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(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(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(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(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(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(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(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 lean mass from baseline to follow-up(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 fat mass from baseline to follow-up(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(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(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(Assessed at three time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up))
• Survival from baseline to follow-up(Assessed from baseline (diagnosis) until 3 months after end of treatment (follow-up))
• Change in cardiorespiratory fitness (VO2peak) from baseline to end of treatment(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 Go (TUG)) test) from baseline 3 months after the end of treatment (follow-up)(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(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(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)(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)(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)(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 end of treatment(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(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(Assessed at two time points: (1) at baseline (diagnosis); and 3 months after the end of treatment (follow-up))
• Change in clinical variables (global score of Common Terminology Criteria for Adverse Events [CTCAE]) from baseline to end of treatment(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(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(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(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(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(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(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(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(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(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(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(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(Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up))
• Change in the range of movement (ROM) of the ankle in the relaxed position from baseline to end of treatment(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment))
• Change in left-ventricular (LV) function (LV ejection fraction) from baseline to follow-up(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(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)(Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up))