Effects of Butyrate Against Pediatric Obesity

Study Overview
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Brief Summary
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Worldwide obesity is a public health concern that is defined by the World Health Organization as abnormal or excessive fat accumulation that may impair health. The main drivers of obesity pathogenesis seem to be a long-term of energy discrepancy between too many calories consumed and an increase of sedentary behavior. A growing body of evidence suggests that the set of microbes that live within the digestive tract, making up the gut microbiota (GM), play a metabolic role in energy regulation and substrate metabolism. Various factors can impact GM, one of these are dietary compounds that deeply affect the growth and metabolism of gut bacteria, since fermentation of nutrients is one core function of the intestinal microbes. Among fermentation products an array of small organic metabolites are short-chain fatty acids (SCFAs) acetate, propionate and butyrate. Among SCFAs, the C-4 fatty acid butyrate, the main fuel for the colonocytes, might have a potential in alleviating obesity and related metabolic complications. Butyrate could act as a regulator of body weight: a reasonable speculation is that butyrate acts on components of the energy balance, promoting energy expenditure and/or reducing energy intake. Preclinical studies have shown that butyrate supplementation prevent high-fat diet-induced obesity and it is able to treat obesity. With the sharp increase of obesity prevalence seen in the pediatric population, novel insights are necessary to counteract this epidemic disease, the outcome of the study is to see whether oral butyrate supplementation could exert similar effect in obese children.

Official Title
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Effects of Oral Supplementation of Butyrate in Children With Obesity

Conditions
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Obesity, Childhood

Intervention / Treatment
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* Dietary Supplement: butyrate
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children/adolescents with diagnosis of obesity (BMI >95° percentile for age and sex) observed at Pediatric Section of Department of Translational Medical Sciences (University of Naples Federico II) Exclusion Criteria Age at enrollment <5 or >17 years BMI <95° percentile for age and sex Patients under pharmacological treatment for obesity (metformin) Patients assuming vitamin E, Patients assuming pre-, pro- or synbiotics Simultaneous presence of other chronic diseases unrelated to obesity: cancer, immunodeficiency, cystic fibrosis, allergies, celiac disease, autoimmune diseases, neuropsychiatric disorders, type 1 diabetes, inflammatory bowel diseases, malformations of urinary or gastrointestinal or respiratory tract, chronic lung diseases, genetic and metabolic diseases, chronic hematological diseases. History of surgery for the treatment of obesity Any medical condition that may interfere with participation in this study Participation in other clinical trials still in progress

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Butyrate + standard care for pediatric obesity<br>standard care for pediatric obesity + sodium butyrate (20 mg/kg body weight/day) | Dietary Supplement: butyrate<br>* sodium butyrate (20 mg/kg body weight/day)<br>|
| Placebo Comparator: placebo + standard care for pediatric obesity<br>standard care for pediatric obesity + placebo (cornstarch) | Other: placebo<br>* cornstarch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI z-score change | BMI z-score change at least of ≥ 0.25 | after 6 months from the start of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| waist circumference | mean waist circumference change | after 6 months from the start of intervention | 
| HOMA index change | mean of HOMA index change | after 6 months from the start of intervention | 
| fasting glucose change | mean of fasting glucose change | after 6 months from the start of intervention | 
| fasting insulin change | mean of fasting insulin change | after 6 months from the start of intervention | 
| total cholesterol change | mean of total cholesterol change | after 6 months from the start of intervention | 
| Low density Lipoprotein cholesterol change | mean of Low density Lipoprotein cholesterol change | after 6 months from the start of intervention | 
| High density Lipoprotein cholesterol change | mean of high density Lipoprotein cholesterol change | after 6 months from the start of intervention | 
| plasma triglycerides change | mean of plasma triglycerides change | after 6 months from the start of intervention | 
| micro RNA 221- expression | mean of mir221- expression | after 6 months from the start of intervention | 
| serum ghrelin | mean of serum ghrelin | after 6 months from the start of intervention | 
| serum Interleukin-6 | mean of Interleukin-6 | after 6 months from the start of intervention | 
| composition of the intestinal microbiota (metagenomics characteristics) | evaluation of gut microbiota structure by shotgun analysis | after 6 months from the start of intervention |