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Effect of POSTbiotics Supplementation on Microbiome in OBese Children: the POST-OB Study

Phase 4
Conditions
Childhood Obesity
Interventions
Drug: Immunofos
Other: Promotion of physical activity
Other: Healthy food habits promotion
Registration Number
NCT04151823
Lead Sponsor
University of Milan
Brief Summary

This study evaluates the possible effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, on gut microbiota composition and metabolite production. It also wants to determine whether postbiotics supplementation, combined with interventions to improve diet and lifestyle, reduces adverse metabolic consequences together with their co-morbidities.

All participants will follow a behaviour (promotion of physical activity) and dietary treatment according to Italian dietary guidelines for childhood obesity.

Postbiotics and vitamin D3 will be given orally for four months; patients will be evaluated four months after supplementation and diet-lifestyle intervention and four months after the end of supplementation and after the alone diet-lifestyle intervention with blood testing and echosonography of the liver.

Detailed Description

25-30 Caucasian obese children will be enrolled at the Pediatric Department of San Paolo Hospital - University of Milan.

Stool samples from all enrolled patients at the different time points (t0, before supplementation and diet-lifestyle intervention, t1, four months after supplementation and diet-lifestyle intervention and t2 four months after the end of supplementation and after the alone diet-lifestyle intervention) will be collected and stored at -80°C until the following investigation:

1. study of the microbiota biodiversity by high-throughput sequencing techniques (16S rRNA gene sequencing) in order to establish whether postbiotics could modulate the microbial composition in obese children;

2. analysis of short chain fatty acids concentration by gas-chromatography (GC-FID) in order to monitor the effect of postbiotics intake modulating microbial metabolite production.

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:

1. 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).

2. 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:

1. 8 or more: optimal Mediterranean diet;

2. 4-7: improvement needed to adjust intake to Mediterranean patterns.

3. 3 or less: very low diet quality.

* Hematological and biochemical status including:

1. Complete cell blood count;

2. 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)

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

* Liver ultrasonography will be performed by a single evaluator.

All participants will follow a behavior (promotion of physical activity) and dietary treatment according to Italian dietary guidelines for childhood obesity.

Postbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; fermented fructooligosaccharides from Lactobacillus paracasei strain CNCM I-5220). 2 mk of product will give 1600 UI/die of VIT D3.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Postbiotic &vitamin D3, lifestyle intervention.Promotion of physical activityPostbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; immunofos from Lactobacillus paracasei CNCM I-5220). 2 mL of product will give 1600 UI/die of VIT D3. Healthy living habits will be encouraged at t0, t1 and t2 visit.
Postbiotic &vitamin D3, lifestyle intervention.Healthy food habits promotionPostbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; immunofos from Lactobacillus paracasei CNCM I-5220). 2 mL of product will give 1600 UI/die of VIT D3. Healthy living habits will be encouraged at t0, t1 and t2 visit.
Postbiotic &vitamin D3, lifestyle intervention.ImmunofosPostbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; immunofos from Lactobacillus paracasei CNCM I-5220). 2 mL of product will give 1600 UI/die of VIT D3. Healthy living habits will be encouraged at t0, t1 and t2 visit.
Postbiotic &vitamin D3, lifestyle intervention.Vitamin D3Postbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; immunofos from Lactobacillus paracasei CNCM I-5220). 2 mL of product will give 1600 UI/die of VIT D3. Healthy living habits will be encouraged at t0, t1 and t2 visit.
Primary Outcome Measures
NameTimeMethod
Changes in short chain fatty acids production by gut microbiotat0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in gut microbiota compositiont0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Secondary Outcome Measures
NameTimeMethod
Changes in LDL-cholesterol levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in HDL-cholesterol levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in body mass indext0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in triglycerides levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Apoprotein B levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in systemic arterial blood pressuret0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Bristol stool chartt0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in fasting insulin levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Apoprotein A1 levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in puberal staget0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in fasting glucose levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in oral glucose tolerance test resultst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in alanine aminotransferase (ALT) levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in aspartate aminotransferase (AST) levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Gamma-glutamyl transferase (GGT) levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in complete cell blood countt0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Homeostasis Model Assessment (HOMA) indext0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Echosonographic changes in liver morphology (degree of steatosis)t0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in total cholesterol levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in Quantitative Insulin-Sensitivity Check Index (QUICKI)t0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in erythrocyte sedimentation rate (ESR)t0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in C-reactive protein (CRP) levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in fecal calprotectin levelst0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in body mass composition assessed with air displacement plethysmography systemt0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in body circumference (waist, left arm)t0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Changes in body skinfold thickness (waist, posterior skinfold and anterior skinfold of left arm)t0: 0 t1: +4 months t2: +8 months

Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).

Trial Locations

Locations (1)

Ospedale San Paolo

🇮🇹

Milan, Italy

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