Evaluation of Intestinal Microbiome in Obese Kids

NCT ID: NCT00816296

Last Updated: 2015-08-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2008-10-31

Study Completion Date

2012-10-31

Brief Summary

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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

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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.

Conditions

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Obesity Non-Alcoholic Fatty Liver Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Controls

Obese (BMI\>30) and normal AST and ALT. Between the ages of 5 and 18 years old.

Blood Draw

Intervention Type OTHER

2 tablespoons of blood will be drawn from participants at study entry, 3 months after study entry, and 6 months after study entry.

Stool collection

Intervention Type OTHER

Stool will be collected from participants 3 times during the study -- at study entry, 3 months from study entry, and 6 months after study entry.

BodPod Measurement

Intervention Type OTHER

Body composition will be measured using a BodPod at study entry, 3 months after study entry, and 6 months after study entry.

Liver Ultrasound

Intervention Type OTHER

A liver ultrasound will be performed at study entry and 6 months after study entry.

Liver Disease

Obese (BMI\>30) and elevated AST and/or ALT (evidence of NAFLD). Between the ages of 5 and 18 years old.

Blood Draw

Intervention Type OTHER

2 tablespoons of blood will be drawn from participants at study entry, 3 months after study entry, and 6 months after study entry.

Stool collection

Intervention Type OTHER

Stool will be collected from participants 3 times during the study -- at study entry, 3 months from study entry, and 6 months after study entry.

BodPod Measurement

Intervention Type OTHER

Body composition will be measured using a BodPod at study entry, 3 months after study entry, and 6 months after study entry.

Liver Ultrasound

Intervention Type OTHER

A liver ultrasound will be performed at study entry and 6 months after study entry.

Interventions

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Blood Draw

2 tablespoons of blood will be drawn from participants at study entry, 3 months after study entry, and 6 months after study entry.

Intervention Type OTHER

Stool collection

Stool will be collected from participants 3 times during the study -- at study entry, 3 months from study entry, and 6 months after study entry.

Intervention Type OTHER

BodPod Measurement

Body composition will be measured using a BodPod at study entry, 3 months after study entry, and 6 months after study entry.

Intervention Type OTHER

Liver Ultrasound

A liver ultrasound will be performed at study entry and 6 months after study entry.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

5 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical College of Wisconsin

OTHER

Sponsor Role lead

Responsible Party

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Medical College of Wisconsin

Principal Investigators

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Vincent Biank, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital and Health System Foundation, Wisconsin

Locations

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Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999 Dec;30(6):1356-62. doi: 10.1002/hep.510300604.

Reference Type BACKGROUND
PMID: 10573511 (View on PubMed)

Iacobellis A, Marcellini M, Andriulli A, Perri F, Leandro G, Devito R, Nobili V. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis. World J Gastroenterol. 2006 Dec 28;12(48):7821-5. doi: 10.3748/wjg.v12.i48.7821.

Reference Type BACKGROUND
PMID: 17203527 (View on PubMed)

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.

Reference Type BACKGROUND
PMID: 17183312 (View on PubMed)

Li Z, Soloski MJ, Diehl AM. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology. 2005 Oct;42(4):880-5. doi: 10.1002/hep.20826.

Reference Type BACKGROUND
PMID: 16175608 (View on PubMed)

Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, Martines D. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G518-25. doi: 10.1152/ajpgi.00024.2006. Epub 2006 Oct 5.

Reference Type BACKGROUND
PMID: 17023554 (View on PubMed)

Fields DA, Goran MI, McCrory MA. Body-composition assessment via air-displacement plethysmography in adults and children: a review. Am J Clin Nutr. 2002 Mar;75(3):453-67. doi: 10.1093/ajcn/75.3.453.

Reference Type BACKGROUND
PMID: 11864850 (View on PubMed)

Nicholson JC, McDuffie JR, Bonat SH, Russell DL, Boyce KA, McCann S, Michael M, Sebring NG, Reynolds JC, Yanovski JA. Estimation of body fatness by air displacement plethysmography in African American and white children. Pediatr Res. 2001 Oct;50(4):467-73. doi: 10.1203/00006450-200110000-00008.

Reference Type BACKGROUND
PMID: 11568289 (View on PubMed)

Other Identifiers

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GC 727

Identifier Type: -

Identifier Source: secondary_id

CHW 08/159

Identifier Type: -

Identifier Source: org_study_id

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