Mediterranean Enriched Diet for Tackling Youth Obesity

Study Overview
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Brief Summary
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The prevalence of obesity is one of the main public health problems worldwide, reaching 18% among young people between 5 and 19 years of age in 2016. One possibility of effective treatment can be the Mediterranean diet (MD). Therefore, it is proposed to carry out a nutritional intervention based on this diet to more effectively reduce obesity in adolescents. The main purpose of this multicentre study is to assess whether an energy-restricted Mediterranean-style diet (MD) intervention including healthy products from the Mediterranean basin (mixed nuts, pomegranate and hummus) and sourdough bread is more effective against obesity and associated CVD risk factors than a conventional low-fat diet carrying out a multicentre nutritional and clinical intervention study specifically targeting obese/overweight adolescents (13-17y) from different Mediterranean countries; all combined with an educational web-application designed to encourage healthy behaviours. It is a multicenter, randomized, controlled intervention study conducted with adolescents with obesity/overweight ≥90 percentile who do not suffer from any chronic disease. 240 subjects will be recruited from three Mediterranean countries: Italy (Parma), Portugal (Coimbra) and Spain (Reus), specifically 80 participants per country, 40 adolescents as an intervention group and 40 as a control group, in Reus. The intervention study is scheduled to begin in January 2021. The intervention group will receive a diet based on the characteristics of MD, and will be reinforced with satisfying and healthy Mediterranean foods such as sourdough bread (2 servings of 50-60g / day), squeezed pomegranate (4 servings of 200ml / week), hummus/chickpeas (2 portions of chickpeas of 150-200g / week, one in hummus format) and mixed nuts (4 servings of 30g / week); and the control group will receive a recommended diet based on the consumption of low-fat foods. A caloric restriction of 20% of the total energy requirements will be applied to both groups in adolescents with BMI ≥95 percentile (obesity) and a caloric restriction <20% of the total energy requirements will be applied in adolescents with BMI ≥90 to <95th percentile according to overweight (gender/age / physical activity). The diet will be applied for 4 months in both groups. Adolescents from both groups will be given a motivational interview and will be provided with an educational website that will be used during the intervention, through which they will learn.

Detailed Description
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The principal outcome is BMI z-score, a standardized measure of BMI based on the specific age and gender norms. The effectiveness of the intervention will be evaluated by comparing the BMI z-score between the control (low-fat diet) and intervention (MD) groups. The secondary outcomes are: Adherence to the DM, KidMed questionnaire; Level of physical activity, PAQ-A questionnaire; Habit/food intake: 3-day dietary record, Helena study food frequency questionnaire, Knowledge about food and nutrition, a questionnaire from Helena's study; Quality of life, kid screen-27 Index; Sociodemographic data of the parents; Anthropometric data: weight, height, BMI, body composition, waist circumference, waist-hip ratio; Clinical variables: blood pressure, Biochemical variables and omic determinations: in urine, blood and feces. In total, the adolescents will receive 5 visits: 1 pre-selection visit (to check inclusion / exclusion criteria in the study) (V0) 1 inclusion visit (V1) in which stool, urine, and blood samples will be collected, anthropometric measurements (such as weight and waist circumference) and blood pressure will be taken, and questionnaires and records will be answered dietary. 1 follow-up visit (V2), at 2 months, in which anthropometric and blood pressure measurements will be taken and questionnaires and dietary records will be answered. 1 final visit (V3), at 4 months, in which stool, urine, and blood samples will be collected, anthropometric and blood pressure measurements will be made, and questionnaires and dietary records will be answered. 1 post-intervention follow-up visit (V4), 4 months after the end of the intervention, in which anthropometric and blood pressure measurements will be taken and questionnaires and dietary records will be answered.

Official Title
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Mediterranean Enriched Diet for Tackling Youth Obesity

Conditions
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Obesity, Adolescent, Lifestyle, Healthy, Diet, Healthy, Cardiovascular Risk Factor

Intervention / Treatment
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* Other: Diet and behavioural intervention
* Other: Diet and behavioural intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: boys and girls aged 13-17 years having obesity, defined as an age- and sex-specific BMI in the 95th percentile or greater (1), or great overweight (age- and sex-specific BMI in the ≥90th to <95th percentile), having informed consent (sign by both, one parent and the adolescent), and to have a mobile phone with internet access. Exclusion Criteria: having diabetes and other metabolic, endocrine and chronic disorders; intake of antibiotics, drug, probiotics or nutritional supplements in the last month; prescribed medicine to control hypertension, inflammation or dyslipidemia, following a prescribed diet for any reason, including weight loss, in the last 3 months; following a religion-restricted diet; and having allergies or food intolerances in: nuts, pomegranate, bread and/or chickpeas.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicentre, blind, single-randomized, parallel, clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mediterranean diet group<br>1) The MD will be based on high consumption of unsaturated fat from vegetable sources (virgin olive oil and nuts) and minimally processed plant foods (vegetables, fruits, nuts, whole grains and legumes), low consumption of meat (especially red and processed meats) and sweets, and moderate consumption of fish and dairy products (mainly yoghurt and cheese). Accordingly, this diet will provide a high amount of mono and polyunsaturated fatty acids, fibre and phenolic compounds. Adolescents in the MD group will replace the intake of conventional breads by sourdough bread consumption (2 servings of 50-60 g daily) and incorporate into their diet chickpeas (2 servings of 150 g/week chickpeas, minimum one of them in hummus format), and they will consume at least another serving of legumes which can be chickpeas or another legume), pomegranate juice (4 servings of 200ml/week) and mixed nuts (4 servings of 30 g/week). | Other: Diet and behavioural intervention<br>* Intervention will receive a specific diet designed following the characteristics of Mediterranean Diet<br>* Other names: MEDITERRANEAN DIET;|
| Active Comparator: Low-fat diet group<br>2) The low-fat diet (control diet) will be based on low consumption of fats. A low-fat diet is the most used diet for obesity treatment in adolescents. This group will not receive any additional specific food by researchers. This diet will be based on the diet proposed as low-fat diet in the PREDIMED study | Other: Diet and behavioural intervention<br>* Control group will receive a specific diet designed following the characteristics of Low fat Diet.<br>* Other names: LOW-FAT DIET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline BMI z-score at 4 months and 8 months | The principal outcome is BMI z-score, a standardized measure of BMI based on the specific age and gender norms. The effectiveness of the intervention will be evaluated by comparing the BMI z-score between the control (low-fat diet) and intervention (MD) groups. | 4 months and 4 months after study cessation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Adherence to the Mediterranean Diet at 4 and 8 months | Change of Adherence to the Mediterranean Diet using KIDMED test by comparing control between the intervention group Scores: =<3 points: Very low-quality diet 4 to 7 points: Need to improve the eating pattern to fit the model Mediterranean. =>8 points: Optimal Mediterranean diet | 4 months and 4 months after study cessation | 
| Change from baseline Level of physical activity at 4 and 8 months | Change of Physical Activity using the Physical Activity Questionnaire test by comparing control between the intervention group A score 1 indicates low physical activity whereas a score of 5 indicates high physical activity | 4 months and 4 months after study cessation | 
| Change from baseline Habit/food intake at 4 and 8 months | Change of Habit/food intake using 3-day dietary record, Helena study food frequency questionnaire by comparing control between intervention group | 4 months and 4 months after study cessation | 
| Change from baseline Knowledge about food and nutrition intake at 4 and 8 months | Change of Knowledge about food and nutrition intake using Helena's study knowledge questionnaire by comparing control between intervention group | 4 months and 4 months after study cessation | 
| Change from baseline Life quality at 4 and 8 months | Change of life quality using kidscreen-27 Index by comparing control between intervention group | 4 months and 4 months after study cessation | 
| Sociodemographic data of the parents one time frame | Sociodemographic data of the parents will be assessed at baseline of study using Healthy Behaviour in School Age Children. Sociodemographic data will be divided by low, medium or high socioeconomic level. | 1 time frame | 
| Change from baseline BMI data at 4 and 8 months | BMI will be assessed by weight (kg) / height (m2), and using Centers for Disease Control and Prevention (CDC) BMI percentiles and will be compared between control and intervention group. | 4 months and 4 months after study cessation | 
| Change from baseline waist circumference data at 4 and 8 months | Waist circumference (cm) will be evaluated and will be compared between control and intervention group. | 4 months and 4 months after study cessation | 
| Change from baseline Waist-hip ratio data at 4 and 8 months | Waist-hip ratio will be evaluated by waist and hip circumference and will be compared between control and intervention group. | 4 months and 4 months after study cessation | 
| Change of Gut-derived metabolites (LPS, SCFAs, lactate, bile acids) | Gut-derived metabolites of both groups will be evaluated by Faeces and/or plasma using NMR /GC-MS | 4 months | 
| Change of biomarkers of oxidative stress (8-OHdG, F2-isoprostanes) | Biomarkers of oxidative stres of both groups will be evaluated by urine using ELISA | 4 months | 
| Change of biomarkers of inflammation (IL-6, CRP, TNFα, MCP1, IL-8) | Biomarkers of inflammation of both groups will be evaluated by plasma using Magnetic bead-based multiplex assays Homeostatic Model Assessment for insulin resistance | 4 months | 
| Change of biomarkers of adipose tissue function (adiponectin, leptin, resistin) | Biomarkers of adipose tissue function of both groups will be evaluated by plasma using Magnetic bead-based multiplex assays Homeostatic Model Assessment for insulin resistance | 4 months | 
| Change of Biomarkers of insulin resistance | Biomarkers of insulin resistance of both groups will be evaluated by plasma using Magnetic bead-based multiplex assays Homeostatic Model Assessment for insulin resistance | 4 months | 
| Change of biomarkers of cardiovascular risk (TMAO) | Biomarkers of cardiovascular risk of both groups will be evaluated by plasma and urine using UHPLC MS | 4 months | 
| Change of circulating levels of glucose and blood lipid profile | Circulating levels of glucose and blood lipid profile of both groups will be evaluated using Enzymatic assays | 4 months | 
| Change of Food Intake biomarkers | Food Intake biomarkers of both groups will be evaluated by urine using Metabolomics (UHPLC MS) | 4 months | 
| Change of Advanced glycation end products (AGEs) related analyses | Advanced glycation end products will be assessed by plasma or erythrocytes using ELISA / enzymatic assays | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Youth Obesity, Mediterranean diet, Interventional study, Healthy lifestyles, Educational approach