Evaluation of Intestinal Microbiome in Obese Kids

Withdrawn

• Conditions: Obesity; Non-Alcoholic Fatty Liver Disease
• Interventions: Other: Blood Draw; Other: Stool collection; Other: BodPod Measurement; Other: Liver Ultrasound

• Registration Number: NCT00816296
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

The goal of this study is to investigate comparisons between the intestinal microbiome in patients with obesity and in patients with obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). With this protocol we hope to better understand how the microbiome of each individual works with disease progression.

Detailed Description

The goal of this study is to investigate and compare the composition of the intestinal microbiome in patients with obesity only to patients with obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). In addition, we will investigate the relationship between alterations in the intestinal microbiome, immune activation, and the progression of NAFLD to Non-Alcoholic Steatohepatitis (NASH). We hypothesize that alterations in the intestinal microbiome are associated with increased immune activation and progression of obesity associated NAFLD. Based on this hypothesis we propose the following aims:

Aim 1. Identify and enroll pediatric cohort with obesity or obesity/NAFLD to study the role of the intestinal microbiome on the development of NAFLD.

1. Enroll participants through the NEW Kids program for treatment of pediatric obesity at Children's Hospital of Wisconsin (CHW). Identify and classify participants through initial clinical evaluation, collect clinical metadata, and obtain and process blood and stool samples for analysis. Demonstrate feasibility by showing that participants can be recruited and participate in the specific study protocol.

2. Follow study population through nutritional/exercise intervention, with follow up collection of clinical data, stool, and blood samples.

Aim 2. Characterize the intestinal microbiome through quantitative PCR and high throughput sequencing analysis of stool specimens in participants with obesity and obesity/NAFLD.

1. Demonstrate feasibility by showing that sampling aliquots from patient fecal samples can be successfully analyzed by proposed methods and yield consistent results for duplicate samples.

2. Compare sequencing results and metagenomic analysis for study groups with particular attention to bacterial composition and metabolic capacity associated with energy harvest, lipid and carbohydrate transport, enhancement of epithelial barrier integrity, and choline metabolism.

3. Investigate whether intervention (nutritional/exercise) results in longitudinal alterations in the intestinal microbiome.

Aim 3. Characterize evidence of systemic inflammation by C-reactive protein (CRP), Tumor necrosis factor alpha (TNF-alpha)Transforming growth factor beta 1 (TGF-beta and LPS Binding Protein (LBP) levels, and analyze results in relationship to the intestinal microbiome and the presence of NAFLD.

1. Compare levels of systemic inflammatory markers of participants with obesity vs. obesity/NAFLD

2. Investigate whether intervention (nutritional/exercise) results in longitudinal alterations in systemic inflammation.

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2008-12-30
• Study First Submitted QC: 2008-12-30
• Study First Posted: 2009-01-01
• Primary Completion: 2011-10
• Study Completion: 2012-10
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-21
• Last Update Posted: 2015-08-24

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age 5-18 Years old
• Willing to consent/undergo necessary procedures
• Obese (BMI>30)
• Speak English or Spanish

Exclusion Criteria

• any other causes of liver disease
• any chronic illnesses or life threatening conditions

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Liver Disease	Liver Ultrasound	Obese (BMI\>30) and elevated AST and/or ALT (evidence of NAFLD). Between the ages of 5 and 18 years old.
Liver Disease	Blood Draw	Obese (BMI\>30) and elevated AST and/or ALT (evidence of NAFLD). Between the ages of 5 and 18 years old.
Liver Disease	Stool collection	Obese (BMI\>30) and elevated AST and/or ALT (evidence of NAFLD). Between the ages of 5 and 18 years old.
Liver Disease	BodPod Measurement	Obese (BMI\>30) and elevated AST and/or ALT (evidence of NAFLD). Between the ages of 5 and 18 years old.
Controls	Blood Draw	Obese (BMI\>30) and normal AST and ALT. Between the ages of 5 and 18 years old.
Controls	BodPod Measurement	Obese (BMI\>30) and normal AST and ALT. Between the ages of 5 and 18 years old.
Controls	Stool collection	Obese (BMI\>30) and normal AST and ALT. Between the ages of 5 and 18 years old.
Controls	Liver Ultrasound	Obese (BMI\>30) and normal AST and ALT. Between the ages of 5 and 18 years old.

Primary Outcome Measures

Name	Time	Method
Alterations in the intestinal microbiome are associated with increased immune activation and progression of obesity associated NAFLD.	3 years

Secondary Outcome Measures

Name	Time	Method
Characterize the intestinal microbiome through quantitative analysis of stool samples in participants with obesity and those with obesity and NAFLD.	3 years
Characterize inflammatory markers of participants with obesity versus those obese participants that also have NAFLD.	3 years

Trial Locations

Locations (1)

Children's Hospital of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States