Biomarkers of Physical Activity/Health in Children and Adolescents

Study Overview
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Brief Summary
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This clinical trial is aimed to recruit a core cohort of children and adolescents, and to perform an educational intervention and follow-up study in a subgroup of volunteers from this core cohort, to obtain specific measurements and samples of interest in these volunteers that will be used for identification and validation of the biomarkers of physical activity (PA) and health.

Detailed Description
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Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. Childhood and adolescence are critical periods for life-time health; processes underlying cardiovascular diseases and obesity generally originate in early ages. However, it is not clear how PA links to different parameters of health. There is an important need to cover this critical gap and, more specifically, to have biomarkers allowing to relate the degree of PA with effects on health. INTEGRActiv addresses this new scientific and societal challenge by focusing on the identification of integrated markers reflecting both aspects - PA level and health - in children and adolescents, which represent an important target population to address personalized interventions to improve future, life long, metabolic health. Identification of new biomarkers will be achieved by combining measures of PA and cardiorespiratory and muscular fitness with anthropometric measures, cardiovascular risk factors and endocrine markers, cytokines, circulating miRNA, and gene expression profile in blood cells and metabolomics profile in plasma and blood cells. Following identification in a core cohort and data integration analysis, candidate biomarkers will be further assessed in core cohort subjects after educational intervention and in existing samples from other independent studies. INTEGRActiv encompasses relevant progress beyond the state-of-the-art for a) the definition of potential biomarkers for PA level in childhood and adolescence; b) the provision of relevant mechanistic information for the link between PA and metabolic health in youth subjects; c) the identification of factors such as age, gender, body weight, sleep behavior and puberal status that quantitatively affect biomarker responses; d) the use and development of new tools in biomarker research, including integrative analysis; e) further assessment and first-step validation of promising candidate biomarkers in an intervention study and other independent studies. It is expected that new identified robust biomarkers reflecting PA level and its relation with health will guide nutritional/life-style and clinical advice and public policies related to endorse biomarker- based personalised PA, with a better adherence and response, to promote health and prevent disease risk factors since early stages of life.

Official Title
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Identification and Validation of Integrative Biomarkers of Physical Activity Level and Health in Children and Adolescents

Conditions
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Physical Activity

Intervention / Treatment
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* Behavioral: Educational intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian children/adolescents with age between 8-10 years for the prepubertal and 13-15 years for the postpubertal groups BMI z-score between those established by the World Health Organization for the subgroups with NW, OW or OB Exclusion Criteria: Children/adolescents with reported pathologies Clinical recommendations against performance of physical activity Presence of eating disorders

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An educational intervention to improve physical activity and promote healthy dietary habits will be carried out in two groups of children/adolescents: (1) a prepubertal group and (2) a postpubertal group. Within each group, there will be volunteers with normal weight (NW), overweight (OW), and obesity (OB). A total of 180 volunteers will be assessed for eligibility (90 for each group), and 60 of them (30 for each group) will be allocated to study (intervention study).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prepubertal group: Educational intervention<br>An educational intervention to improve physical activity and promote healthy dietary habits will be carried out in prepubertal (8-10 years) volunteers with normal weight (NW), overweight (OW), and obesity (OB). | Behavioral: Educational intervention<br>* The intervention will consist of recommendations to improve physical activity (PA) and dietary habits. It is based on the PAIDO Programme (www.programapaido.es), an outpatient family-based multidisciplinary programme that combines PA, education on nutrition, and behavioural therapy. It will last 6 months and improvement of metabolic health and body weight loss is expected, particularly in the groups with overweight and obesity. The dietary intervention will be focused on the promotion of the Mediterranean diet, with follow-up and advice from a dietitian-nutritionist. Participants will be encouraged in reducing sedentary behaviour (watching television, playing computer games, playing board games). Performance of aerobic and strength physical exercises will be scheduled, progressively increasing the intensity. Volunteers and their parents will participate in monthly sessions to follow-up on adherence to the PA and dietary recommendations and give personalized advice.<br>|
| Experimental: Postpubertal group: Educational intervention<br>An educational intervention to improve physical activity and promote healthy dietary habits will be carried out in postpubertal (13-15 years) volunteers with normal weight (NW), overweight (OW), and obesity (OB). | Behavioral: Educational intervention<br>* The intervention will consist of recommendations to improve physical activity (PA) and dietary habits. It is based on the PAIDO Programme (www.programapaido.es), an outpatient family-based multidisciplinary programme that combines PA, education on nutrition, and behavioural therapy. It will last 6 months and improvement of metabolic health and body weight loss is expected, particularly in the groups with overweight and obesity. The dietary intervention will be focused on the promotion of the Mediterranean diet, with follow-up and advice from a dietitian-nutritionist. Participants will be encouraged in reducing sedentary behaviour (watching television, playing computer games, playing board games). Performance of aerobic and strength physical exercises will be scheduled, progressively increasing the intensity. Volunteers and their parents will participate in monthly sessions to follow-up on adherence to the PA and dietary recommendations and give personalized advice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI Z-score | BMI z-score will be calculated from height and weight data, considering age and sex, following World Health Organization (WHO) guidelines. | Baseline (all groups) | 
| BMI Z-score | BMI z-score will be calculated from height and weight data, considering age and sex, following WHO guidelines. | 3 months (all groups) | 
| BMI Z-score | BMI z-score will be calculated from height and weight data, considering age and sex, following WHO guidelines. | 6 months (all groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weight (kg) | Baseline (all groups) | 
| Weight | Weight (kg) | 3 months (all groups) | 
| Weight | Weight (kg) | 6 months (all groups) | 
| Height | Height (m) | Baseline (all groups) | 
| Height | Height (m) | 3 months (all groups) | 
| Height | Height (m) | 6 months (all groups) | 
| Waist circumference | Waist circumference (cm) | Baseline (all groups) | 
| Waist circumference | Waist circumference (cm) | 3 months (all groups) | 
| Waist circumference | Waist circumference (cm) | 6 months (all groups) | 
| Body composition | Lean and fat mass (in %) measured using bioimpedance | Baseline (all groups) | 
| Body composition | Lean and fat mass (in %) measured using bioimpedance | 3 months (all groups) | 
| Body composition | Lean and fat mass (in %) measured using bioimpedance | 6 months (all groups) | 
| Blood pressure | Systolic and diastolic pressure will be measured (mm Hg) | Baseline (all groups) | 
| Blood pressure | Systolic and diastolic pressure will be measured (mm Hg) | 3 months (all groups) | 
| Blood pressure | Systolic and diastolic pressure will be measured (mm Hg) | 6 months (all groups) | 
| Handgrip strength | Handgrip strength from right and left hands (Kg). This measure will be used, together with standing broad jump tests to assess musculoskeletal fitness. | Baseline (all groups) | 
| Standing long jump | Standing long jump (cm). This measure will be used, together with handgrip strenght to assess musculoskeletal fitness. | Baseline (all groups) | 
| Cardiorespiratory Fitness (CRF) | CRF will be measured as maximal oxygen consumption (V̇O2max) from cardiopulmonary exercise testing, using a treadmill test and the Balke protocol | Baseline (all groups) | 
| Change in the level of physical activity (PA) during 6 months evaluated by accelerometry | Different intensities of PA will be measured during one week before (baselline) and after the intervention (6 months) using accelerometry (actigraph GTX3+) | Change from baseline in physical activity at 6 months (all groups) | 
| Adherence to the Mediterranean diet | Adherence to the Mediterranean diet will be evaluated using the KIDMED, Mediterranean Diet Quality Index in children and adolescents. Score: 0-12. Value of the KIDMED score: ≤3, very-low-quality diet; 4-7, need to improve the food pattern to adjust it to the Mediterranean one; ≥8, optimal Mediterranean diet. | Baseline (all groups) | 
| Adherence to the Mediterranean diet | Adherence to the Mediterranean diet will be evaluated using the KIDMED, Mediterranean Diet Quality Index in children and adolescents. Score: 0-12. Value of the KIDMED score: ≤3, very-low-quality diet; 4-7, need to improve the food pattern to adjust it to the Mediterranean one; ≥8, optimal Mediterranean diet. | 6 months (all groups) | 
| Physical activity (PA) level | PA level will be evaluated using the Questionnaire for Older Children (PAQ-C) and for Adolescents (PAQ-A); score: 0-5 for different levels of PA (no units). | Baseline (all groups) | 
| Physical activity (PA) level | PA level will be evaluated using the Questionnaire for Older Children (PAQ-C) and for Adolescents (PAQ-A); score: 0-5 for different levels of PA (no units). | 6 months (all groups) | 
| Sedentary behaviour | Sedentary behaviour will be evaluated using a Screen Time Questionnaire (STQ). The total screen hours will ba obtained by measuring: hours of daily TV, weekend TV, daily Computer, weekend computer, daily videogames, weekend videogames, daily free internet, weekend free internet, daily study internet, weekend study internet, and weekend study. | Baseline (all groups) | 
| Sedentary behaviour | Sedentary behaviour will be evaluated using a Screen Time Questionnaire (STQ). The total screen hours will ba obtained by measuring: hours of daily TV, weekend TV, daily Computer, weekend computer, daily videogames, weekend videogames, daily free internet, weekend free internet, daily study internet, weekend study internet, and weekend study. | 6 months (all groups) | 
| Sleep habits | Sleep habits will be evaluated using the Pediatric Sleep Questionnaire (PSQ) (no units). | Baseline (all groups) | 
| Sleep habits | Sleep habits will be evaluated using the Pediatric Sleep Questionnaire (PSQ) (no units). | 6 months (all groups) | 
| Eating disorders - SCOFF Questionnaire | SCOFF questionnaire for the screening of eating disorders in primary care. Units: SCOFF score. Score>2, positive screening | Baseline (all groups) | 
| Eating disorders - SCOFF Questionnaire | SCOFF questionnaire for the screening of eating disorders in primary care. Units: SCOFF score. Score>2, positive screening | 6 months (all groups) | 
| Eating disorders- DEBQ Questionnaire | Dutch Eating Behavior Questionnaire for Children (DEBQ-C). Units: DEBQ score. The questionnaire measures three eating behaviors: emotional, external and restrained. | Baseline (all groups) | 
| Eating disorders- DEBQ Questionnaire | Dutch Eating Behavior Questionnaire for Children (DEBQ-C). Units: DEBQ score. The questionnaire measures three eating behaviors: emotional, external and restrained. | 6 months (all groups) | 
| Plasma glucose | Gucose (mg/dL) | Baseline (all groups) | 
| Plasma glucose | Gucose (mg/dL) | 6 months (all groups) | 
| Plasma insulin | Insulin (mg/dL) | Baseline (all groups) | 
| Plasma insulin | Insulin (mg/dL) | 6 months (all groups) | 
| Plasma triglycerides (TG) | TG (mg/dL) | Baseline (all groups) | 
| Plasma triglycerides (TG) | TG (mg/dL) | 6 months (all groups) | 
| Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) | Total cholesterol, HDL-C and LDL-C (mg/dL) | Baseline (all groups) | 
| Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) | Total cholesterol, HDL-C and LDL-C (mg/dL) | 6 months (all groups) | 
| Plasma uric acid | Uric acid (mg/dL) | Baseline (all groups) | 
| Plasma uric acid | Uric acid (mg/dL) | 6 months (all groups) | 
| Plasma creatinine | Creatinine (mg/dL) | Baseline (all groups) | 
| Plasma creatinine | Creatinine (mg/dL) | 6 months (all groups) | 
| Insulin resistance | Insulin resistance will be assessed by the homeostatic model assessment (HOMA) index | Baseline (all groups) | 
| Insulin resistance | Insulin resistance will be assessed by the homeostatic model assessment (HOMA) index | 6 months (all groups) | 
| Analysis of additional circulating metabolites | Metabolites (including myokines and adipokines) will be assessed using commercial enzyme-linked immunosorbent assays (ELISA) | Baseline (all groups) | 
| Analysis of additional circulating metabolites | Metabolites (including myokines and adipokines) will be assessed using commercial enzyme-linked immunosorbent assays (ELISA) | 6 months (all groups) | 
| Transcriptome analysis | Transcriptome analysis will be performed with RNA Sequencing (RNA-Seq) using next-generation sequencing platforms in peripheral blood cells (PBC) | Baseline (all groups) | 
| Transcriptome analysis | Transcriptome analysis will be performed with RNA Sequencing (RNA-Seq) using next-generation sequencing platforms in peripheral blood cells (PBC) | 6 months (all groups) | 
| Circulating miRNA | Circulating miRNA will be analysed using miRCURY LNA miRNA miRNome PCR Panels (Qiagen) | Baseline (all groups) | 
| Circulating miRNA | Circulating miRNA will be analysed using miRCURY LNA miRNA miRNome PCR Panels (Qiagen) | 6 months(all groups) | 
| Evaluation of metabolomics and lipidomics | Untargeted and targeted metabolomics and lipidomics will also be performed in plasma using liquid chromatography - mass spectrometry-based (LC-MS) methods. | Baseline (all groups) | 
| Evaluation of metabolomics and lipidomics | Untargeted and targeted metabolomics and lipidomics will also be performed in plasma using liquid chromatography - mass spectrometry-based (LC-MS) methods. | 6 months (all groups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Integration analysis, Cardiorespiratory fitness, Metabolomics, Transcriptomics, miRNome, Adipokines, Cytokines, Biomarkers