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

• ClinicalTrials.gov Identifier: NCT04151823
• Recruitment Status: Unknown
• First Posted: November 5, 2019
• Last Update Posted: July 28, 2020
• Sponsor: University of Milan
• Information provided by (Responsible Party): Elvira Verduci, University of Milan

Tracking Information

• First Submitted Date: October 30, 2019
• First Posted Date: November 5, 2019
• Last Update Posted Date: July 28, 2020
• Actual Study Start Date: January 7, 2019
• Estimated Primary Completion Date: January 7, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2019)

• Changes in gut microbiota composition [ Time Frame: 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 short chain fatty acids production by gut microbiota [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 1, 2019)

• Changes in HDL-cholesterol levels [ Time Frame: 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 LDL-cholesterol levels [ Time Frame: 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 triglycerides levels [ Time Frame: 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 systemic arterial blood pressure [ Time Frame: 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 mass index [ Time Frame: 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 Bristol stool chart [ Time Frame: 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 puberal stage [ Time Frame: 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 fasting glucose levels [ Time Frame: 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 fasting insulin levels [ Time Frame: 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 oral glucose tolerance test results [ Time Frame: 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 Apoprotein A1 levels [ Time Frame: 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 Apoprotein B levels [ Time Frame: 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 alanine aminotransferase (ALT) levels [ Time Frame: 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 aspartate aminotransferase (AST) levels [ Time Frame: 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 Gamma-glutamyl transferase (GGT) levels [ Time Frame: 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 complete cell blood count [ Time Frame: 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 levels [ Time Frame: 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 Homeostasis Model Assessment (HOMA) index [ Time Frame: 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 Quantitative Insulin-Sensitivity Check Index (QUICKI) [ Time Frame: 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) [ Time Frame: 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) levels [ Time Frame: 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 fecal calprotectin levels [ Time Frame: 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).
• Echosonographic changes in liver morphology (degree of steatosis) [ Time Frame: 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 mass composition assessed with air displacement plethysmography system [ Time Frame: 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 circumference (waist, left arm) [ Time Frame: 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) [ Time Frame: 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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of POSTbiotics Supplementation on Microbiome in OBese Children: the POST-OB Study
• Official Title: Effect of POSTbiotics Supplementation on Microbiome in OBese Children: the POST-OB Study

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Childhood Obesity

Intervention

• Drug: Vitamin D3
  2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN: 2 mL of product will give 1600 UI/die of VIT D3.
• Drug: Immunofos
  Postbiotics will be given at the dose of 80 mg/day. immunofos from Lactobacillus paracasei CNCM I-5220).
• Other: Promotion of physical activity
  Promotion of physical activity will be encouraged at t0, t1, t2
• Other: Healthy food habits promotion
  Promotion of healthy food habits will be encouraged at t0, t1, t2

Study Arms

Experimental: Postbiotic &vitamin D3, lifestyle intervention.

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; 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.

Interventions:

• Drug: Vitamin D3
• Drug: Immunofos
• Other: Promotion of physical activity
• Other: Healthy food habits promotion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 1, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 7, 2021
• Estimated Primary Completion Date: January 7, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 14 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04151823
• Other Study ID Numbers: 2015/ST/135-2
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Elvira Verduci, University of Milan
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Milan
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Milan
• Verification Date: July 2020