Effect of Docosahexaenoic Acid Supplementation on Microbiome in Obese ChiLdrEn. (DAMOCLE)

Effect of Docosahexaenoic Acid Supplementation on Microbiome in Obese ChiLdrEn. The DAMOCLE Study

Evaluation of the possible effect of DHA supplementation, combined with interventions aimed at improving diet and lifestyle, on gut microbiota composition and metabolite production.

Study Overview

• Status: Unknown
• Conditions: Childhood Obesity
• Intervention / Treatment: Drug: Docosahexaenoic Acid Supplementation; Other: Promotion of physical activity; Other: Promotion of healthy food habits

Detailed Description

Differences in gut microbiota composition and function will be evaluated in obese children before starting the DHA supplementation and dietary-lifestyle intervention, at the end of DHA supplementation (4 months) e after 4 months of dietary dietary-lifestyle intervention without DHA supplementation. The investigators will identify the role of DHA on the intestinal microbiota and indicative species related to insulin resistance (IR). The investigators will determine whether DHA supplementation, combined with interventions to improve diet and lifestyle, reduces adverse metabolic consequences together with their co-morbidities.

The following tasks will be also performed at t0, t1 and t2:

Clinical examination including: physical examination, Tanner score evaluation; Bristol Stool Chart Blood pressure will be checked in all children by using oscillometric devices validated in the pediatric age group.

Anthropometry including body circumferences and skinfolds, calculation of BMI z scores and body composition. Body composition will be assessed using an air displacement plethysmography system (BOD POD COSMED-USA).

Dietary assessment:

• Food intakes will be recorded by prospective 3-d weighed food records obtained with food scales. Parents will be advised on how to record all food and beverages consumed during 2 weekdays and 1 weekend day. Quantification and analysis of the energy intake and nutrient composition will be performed with an ad hoc PC software (MètaDieta®, Me.Te.Da S.r.l., San Benedetto del Tronto, Italy).

• Mediterranean Diet Quality Index (KIDMED) questionnaire for Mediterranean Diet assessment. The KIDMED index ranges from 0 to 12, and is based on a 16-question test that can be self-administered. The sums of the values from the administered test will be classified into three levels:

  8 or more: optimal Mediterranean diet; 4-7: improvement needed to adjust intake to Mediterranean patterns. 3 or less: very low diet quality.

Hematological and biochemical status including:

Complete cell blood count;

Metabolic and nutritional parameters according to local routines for childhood obesity (fasting glucose, fasting insulin, LDL, HDL, total cholesterol, triglycerides, Apolipoprotein A and Apolipoprotein B levels, transaminases and amma-glutamyl transferase). Oral Glucose Tolerance Test (OGTT) will be performed. The insulin sensitivity and insulin resistance was assessed by calculating HOMA index (Homeostasis Model Assessment) and QUICKI (Quantitative Insulin-Sensitivity Check Index), using the following formulas:

HOMA: fasting plasma insulin in mU/l x FPG in mmol/l/22.5 QUICKI: 1/(log10 fasting plasma insulin in mU/l + log10 glucose in mg/dl)

Inflammatory index (VES, high-sensitive CRP, including fecal calprotectin)

Liver ultrasonography for detection of fatty liver disease

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elvira Verduci, PhD; Phone Number: +39 3934771218; Email: elvira.verduci@unimi.it

Study Locations

• Italy
  • Milan, Italy, 20142
    • Recruiting
    • Ospedale San Paolo
    • Contact: Elvira Verduci, MD PhD Assistant Professor; Phone Number: +39 0281844508; Email: elvira.verduci@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 6 <Age <14 years
• Severe obesity (>3 DS) according to WHO classification.
• Gestational age: 37-42 weeks.
• Birth-weight: > 2500 g e < 4000 g
• Caucasian

Exclusion Criteria:

• secondary obesity
• supplementation with pre/probiotics (in the previous 3 months);
• antibiotic treatment (in the previous 3 months);
• chronic or acute intestinal diseases (in the previous 3 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Docosahexaenoic Acid Supplementation, lifestyle intervention; Docosahexaenoic Acid (DHA) will be given at the dose of 500 mg/day. Physical activity and healthy eating habits will be encouraged.

Drug: Docosahexaenoic Acid Supplementation; Docosahexaenoic Acid (DHA) will be given at the dose of 500 mg/day (2 ml per day DHA RICH OIL 25% aroma mandorla FoodAR Limbiate, Italy;50% DHA oil obtained from Schyzochitrium sp ; Martek Biosciences Corporation, Columbia, Maryland, USA) to all participants of the study. DHA 2 ml will provide about 16 kcal of energy.; Other Names: Diet intervention; Lifestyle intervention; Other: Promotion of physical activity; All participants will underwent a visit at t0, t1 and t2 in which physical activity will be promoted according to Italian dietary guidelines for childhood obesity.; Other: Promotion of healthy food habits; All participants will underwent a visit at t0, t1 and t2 in which healthy food habits will be promoted according to Italian dietary guidelines for childhood obesity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiota composition.	Interventions aimed at improving diet and lifestyle, on gut microbiota composition and metabolite production. Differences in gut microbiota composition and function will be evaluated in obese children's stools before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months). Study of the microbiota biodiversity will be performed by high-throughput sequencing techniques (16S rRNA gene sequencing) in order to establish whether postbiotics could modulate the microbial composition in obese children	t0: 0 t1: +4 months t2: +8 months
Changes in short-chain fatty acid production by gut microbiota	Interventions aimed at improving diet and lifestyle, on gut microbiota composition and metabolite production. Differences in gut microbiota composition and function will be evaluated in obese children's stools before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months). Analysis of short chain fatty acids concentration by gas-chromatography (GC-FID) will be performed in order to monitor the effect of postbiotics intake modulating microbial metabolite production	t0: 0 t1: +4 months t2: +8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in total cholesterol levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in LDL cholesterol levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in HDL cholesterol levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in triglycerides levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fasting glucose levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fasting insulin levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in HOMA index (Homeostasis Model Assessment)	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in QUICKI (Quantitative Insulin-Sensitivity Check Index)	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in alanine aminotransferase (ALT) levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in aspartate aminotransferase (ALT) levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in gamma glutamyl transferase (GGT) levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body mass index	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in waist circumference	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in triceps skinfold	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in systemic arterial blood pressure	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Complete cell blood count	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in C-reactive protein (CRP) levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in erythrocyte sedimentation rate (ESR)	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fecal calprotectin levels	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body mass composition	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months). body mass composition will be assessed using an air displacement plethysmography system (BOD POD COSMED-USA)	t0: 0 t1: +4 months t2: +8 months
Oral glucose tolerance test (OGTT) result	Fasting glucose and glucose levels after 2 hours from ingestion of a glucose-containing solution.	t0
Degree of fatty liver disease evaluated by echosonography of the liver	Interventions aimed at improving diet and lifestyle, on anthropometrics data and glucose and lipid profile before starting the DHA supplementation (t0) and dietary-lifestyle intervention, at the end of DHA supplementation (t1: +4 months) and after 4 months of dietary dietary-lifestyle intervention without DHA supplementation (t2: +8 months). body mass composition will be assessed using an air displacement plethysmography system (BOD POD COSMED-USA)	t0: 0 t1: +4 months t2: +8 months

Collaborators and Investigators

• Sponsor: University of Milan
• Investigators: Study Chair: Elvira Verduci, Hospital San Paolo

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Anticipated): May 30, 2021
• Study Completion (Anticipated): May 30, 2021

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Nutrition; Gut microbiota; Childhood obesity; PUFA supplementation
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity
• Other Study ID Numbers: 2015/ST/135-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No