Clinical trial NCT05539794: Exercise and Lifestyle in Adolescent Cancer (HEALTHYADOL)
Official title: Exercise and Lifestyle Intervention for Patients With Adolescent Cancer: a Randomised Controlled Trial (HEALTHYADOL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Adolescent Cancer
Keywords: cancer
lifestyle
cardiac function
Lead sponsor: Universidad Europea de Madrid
Sponsor class: OTHER
First posted: 2022-09-14
Enrollment: 136
Sex: ALL
Minimum age (years): 12
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators will apply a two-arm RCT design, following the Consolidated Standards of Reporting Trials recommendations (1:1 randomisation ratio using a computer-generated random allocation sequence with a block on gender and main tumour type \[leukaemias/solid tumours\])
Primary purpose: TREATMENT

Brief summary: The investigators will study the effects of an inhospital exercise intervention combined with lifestyle--including diet--counselling along the duration of 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 with 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. In addition to usual care, the control group will be informed of the benefits of a healthy lifestyle. The intervention group will follow a physical exercise and lifestyle counselling program. The exercise intervention will be performed in the hospital gymnasium, except for neutropenic phases--during which time sessions will be performed in the patients' ward--and will also include inspiratory muscle training. Health counselling will include a psychological intervention based on motivational interviewing techniques, guidance by a nutritionist, and support sessions with survivors who will share their experiences with the study participants. 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).

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 an inhospital 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 an inhospital exercise intervention combined with lifestyle--including diet--counselling along the duration of 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 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 control group will be informed of the benefits of a healthy lifestyle. 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 inspiratory muscle training (5 days/week). Health counselling will include a psychological intervention (1 session/week) based on motivational interviewing techniques, guidance by a nutritionist (2 sessions/month), and support sessions (1/month) with survivors (≥5-year survivorship) who will share their experiences with the study participants. 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in left-ventricular (LV) function (LV ejection fraction) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in left-ventricular (LV) function (LV ejection fraction) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in left-ventricular (LV) function (LV fractional shortening) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in left-ventricular (LV) function (LV fractional shortening) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
measure: Change in global longitudinal strain (GLS) of the left ventricle from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in global longitudinal strain (GLS) of the left ventricle from baseline to 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
Secondary outcomes:
measure: Change in 'clinic' arterial blood pressure from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
measure: Change in 'clinic' arterial blood pressure from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in serum lipid profile (cholesterol) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
measure: Change in serum lipid profile (cholesterol) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
measure: Change in serum lipid profile (triglycerides) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
measure: Change in serum lipid profile (triglycerides) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)]
measure: Change in adiposity index from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in adiposity index from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow-up)
measure: Change in DXA measures of lean mass from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in DXA measures of lean mass from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in DXA measures of fat mass from baseline to end of tratment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in DXA measures of fat mass from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in DXA measure of bone health from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in DXA measure of bone health from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and 3 months after the end of treatment (follow-up)
measure: Change in cardiorespiratory fitness (VO2peak) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in cardiorespiratory fitness (VO2peak) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in muscle strength from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in muscle strength from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis);and (2) 3 months after the end of treatment (follow-up)
measure: Change in inspiratory muscle strength (PImax) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in inspiratory muscle strength (PImax) from baseline to follow-up
timeFrame: Assessed at three time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Survival from baseline to follow-up
timeFrame: Assessed from baseline (diagnosis) until 3 months after end of treatment (follow-up)
measure: Treatment tolerability from baseline to end of treatment
timeFrame: Assessed from baseline (diagnosis) until 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in clinical variables (days of hospitalization) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
measure: Change in clinical variables (global score of Common Toxicity Criteria for Adverse Events [CTCAE]) from baseline to end of treatment
timeFrame: Assessed continuously (every day) from baseline (diagnosis) until 14 to 28 weeks after diagnosis.
measure: Change in clinical variables (global score of Common Toxicity Criteria for Adverse Events [CTCAE]) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in metabolic markers (glucose) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
measure: Change in metabolic markers (glucose) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Metabolic markers (insulin) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Metabolic markers (insulin) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in metabolic markers (HOMA-IR) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in metabolic markers (HOMA-IR) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in chronic systemic inflammation (high-sensitivity C-reactive protein) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in chronic systemic inflammation (high-sensitivity C-reactive protein) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in plasma cardiometabolic-related targeted proteome from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in plasma cardiometabolic-related targeted proteome from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (i.e., follow-up)
measure: Change in gut microbiome (alpha-diversity) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in gut microbiome (alpha-diversity) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in gut microbiome (beta-diversity) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in gut microbiome (beta-diversity) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in gut microbiome (specific bacteria) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in gut microbiome (specific bacteria) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in Immune phenotype (lymphocyte subpopulations) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis
measure: Change in Immune phenotype (lymphocyte subpopulations) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in Immune phenotype (natural killer (NK) cells) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in Immune phenotype (NK cells) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in Immune function from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in immune function from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from baseline to end of treatment
timeFrame: : Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from baseline to 3 months after the end of treatment (follow-up)
timeFrame: : Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in cardiac troponin I from baseline to end of treatment
timeFrame: : Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in cardiac troponin I from baseline to 3 months after the end of treatment (follow-up)
timeFrame: : Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in left-ventricular (LV) mass from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in left-ventricular (LV) mass from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) and (2) 3 months after the end of treatment (follow-up)
measure: Change in relative wall thickness (RWT) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in relative wall thickness (RWT) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in DXA measures of visceral adipose tissue (VAT) from baseline to end of tratment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in DXA measures of visceral adipose tissue (VAT) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in serum lipid profile (apolipoprotein B) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in serum lipid profile (apolipoprotein B) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis)]
measure: Change in DXA measure of bone health from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in DXA measure of bone health from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and 3 months after the end of treatment (follow-up)
measure: Change in handgrip strength from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in handgrip strength from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis);and (2) 3 months after the end of treatment (follow-up)
measure: Change in interventricular septum thickness (IVS) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in interventricular septum thickness (IVS) from baseline to 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in left-ventricular end-diastolic diameter (LVEDD) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in left-ventricular LV end-diastolic diameter (LVEDD) from baseline to 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in left-ventricular posterior wall thickness (LVPW) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in left-ventricular posterior wall thickness (LVPW) from baseline to 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 3 months after the end of treatment (follow-up)
measure: Change in functional mobility (Timed Up and Go (TUG)) test) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in functional mobility (Timed Up and Go (TUG)) test) from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in functional mobility (Timed Up and Down Stairs (TUDS)) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in functional mobility (Timed Up and Down Stairs (TUDS) test) from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in functional mobility (30-second chair stand test) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in functional mobility (in 30-second chair stand test) from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in health-related quality of life (HRQoL) from baseline to end of treatment.
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in health-related quality of life (HRQoL) from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in fatigue from baseline to end of treatment.
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in fatigue from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in energy and nutrient intake from baseline to end of treatment.
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in energy and nutrient intake from baseline 3 months after the end of treatment (follow-up)
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in body mass index (BMI) from baseline to end of treatment
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); and (2) 14 to 28 weeks after diagnosis (i.e., end of treatment)
measure: Change in body mass index (BMI) from baseline to follow-up
timeFrame: Assessed at two time points: (1) at baseline (diagnosis); (2) 3 months after the end of treatment (follow-up)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: UEM
city: Villaviciosa de Odón
country: Spain
facility: Universidad Europea de Madrid
Study officials:
References: