Influence of the Diversity and Composition of the Microbiota in the Development of Pediatric Fatty Liver

Study Overview
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Brief Summary
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The objectives of the present study are: 1) to identify the intestinal and salivary microbiota associated with the presence and severity of hepatic steatosis in children (Study I: case-control study), and 2) to develop a personalized 12-week intervention program based on diet and exercise to examine its effects on the diversity and composition of the microbiota in children with hepatic steatosis (Study II: intervention study)

Detailed Description
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The MicroKid project will acts first as a case-control study (Study I) in order to identify the hepatic steatosis and intestinal and salivary microbiota in children grouped as non-overweight, obese-non-hepatic steatosis, and obese-hepatic steatosis. Then, an intervention study (Study II) will be developed for those children with obesity (i.e., obese-non-hepatic steatosis, and obese-hepatic steatosis groups). Methodology: A total of 60 children, 8-12 years-old, will be assigned to control (non-overweight children, N= 20), obese-non-hepatic steatosis (children with obesity, but without hepatic steatosis, N=20), and obese-hepatic steatosis (children with obesity and hepatic steatosis, N= 20) groups (Study I: case-control study). The obesity and obesity + hepatic steatosis groups will attend to a 12-weeks healthy lifestyle education program (2 days/month) and home-based exercise program (minimum 3 days/week) (Study II: intervention study). The combined intervention program for the Study II will include: i) healthy lifestyle education program focused on dietary and lifestyle guidelines for both children and parents (2 days/month, 60 min), and ii) exercise program based on high-intensity interval training which combines aerobic and resistance training (at least 3 days/week, from 38 to 44 min). Measurements: In the Study I (i.e., case-control study), all participants will be evaluated at baseline. For the Study II (i.e., intervention study), only those participants that belongs to obese-non-hepatic steatosis and obese-hepatic steatosis groups, will be additionally evaluated after the intervention program (12-week). The following outcomes will be measured: hepatic fat fraction and abdominal adiposity (magnetic resonance imaging), intestinal and salivary microbiota, body composition (bioimpedance), cardiometabolic risk factors, liver enzymes, physical fitness (field-fitness tests), physical activity (accelerometry), sleep (accelerometry), dietary habits (24h recalls, and food frequency questionnaires), and pubertal development and sociodemographic characteristics will be measured.

Official Title
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Influence of the Diversity and Composition of the Microbiota in the Development of Pediatric Fatty Liver: Identification of Biomarkers and Development of Personalized Therapy: The MicroKid Project

Conditions
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Non-Alcoholic Fatty Liver Disease, Obesity, Metabolic Syndrome

Intervention / Treatment
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* Other: Multidisciplinary intervention program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obesity defined based on the sex-and-age specific body mass index standards 8-12 years old Exclusion Criteria: Medical conditions that hamper their participation in the exercise program

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 12 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br> | |
| Active Comparator: Obesity-Non-hepatic steatosis<br>Healthy lifestyle education program focused on dietary and lifestyle guidelines for both children and parents (2 days/month, 60 min), and exercise program based on high-intensity interval training which combine aerobic and resistance training (at least 3 days/week, from 38 to 44 min). | Other: Multidisciplinary intervention program<br>* The intervention program includes an educational program promoting healthy dietary habits and physical activity (nutritionist and exercise physiologist) (2 times/month, for children and parents), and supervised home-based exercise (from 3 to 5 times/week, 38-44 min) program for 12-weeks.<br>|
| Experimental: Obesity-Hepatic steatosis<br>Healthy lifestyle education program focused on dietary and lifestyle guidelines for both children and parents (2 days/month, 60 min), and exercise program based on high-intensity interval training which combine aerobic and resistance training (at least 3 days/week, from 38 to 44 min). | Other: Multidisciplinary intervention program<br>* The intervention program includes an educational program promoting healthy dietary habits and physical activity (nutritionist and exercise physiologist) (2 times/month, for children and parents), and supervised home-based exercise (from 3 to 5 times/week, 38-44 min) program for 12-weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic fat | Hepatic fat fraction measured by magnetic resonance imaging before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Intestinal microbiota | Diversity and composition of intestinal microbiota before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Salivary microbiota | Diversity and composition of salivary microbiota before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visceral adiposity | Visceral adipose tissue measured by magnetic resonance imaging before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Subcutaneous abdominal adiposity | Subcutaneous abdominal adipose tissue measured by magnetic resonance imaging before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Intermuscular abdominal adiposity | Intermuscular abdominal adipose tissue measured by magnetic resonance imaging before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Weight | Weight measured by bioimpedance before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Height | Height measured by stadiometer before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Fat mass | Fat mass measured by bioimpedance before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Fat-free mass | Fat free mass measured by bioimpedance before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Glucose | Glucose measured by blood analysis before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Insulin | Serum insulin concentration measured by ELISA before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Cholesterol | Serum cholesterol measured by spectrophotometry before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Triglycerides | Serum triglycerides measured by spectrophotometry before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Leptin | Plasma leptin concentration measured by ELISA before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Adiponectin | Plasma adiponectin measured by ELISA before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| C-reactive protein | Plasma hs-CRP measured by ELISA before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Waist circumference | Waist circumference measured by non-elastic tape before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Systolic and diastolic blood pressure | Systolic and diastolic blood pressure measured by sphygmomanometer before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Physical fitness | Cardiorespiratory fitness, upper- and lower-limbs, and speed agility measured by the Alpha-fitness battery. | baseline and post-test (12-weeks) | 
| Physical activity and sleep | Physical activity and sleep measured by accelerometry before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| 24h dietary habits | 24h dietary habits assessed by 24h recalls before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 
| Dietary habits history | Dietary habits history assessed by food frequency questionnaires before and after 12-weeks intervention program | baseline and post-test (12-weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic hepatic steatosis, Obesity, Children, Exercise, Diet, Microbiota