Evaluation of Intestinal Microbiome in Obese Kids

Obesity Clinical Trial

Official title:

Evaluation of the Intestinal Microbiome in Obese Children With and Without Non-Alcoholic Fatty Liver Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00816296
• Other study ID #: CHW 08/159
• Secondary ID: GC 727
• Status: Withdrawn
• Phase: N/A
• First received: December 30, 2008
• Last updated: August 21, 2015
• Start date: October 2008
• Est. completion date: October 2012

Study information

• Verified date: August 2015
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 18 Years

Eligibility

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

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease
• Obesity

Intervention

Other:
• 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.
• 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.
• BodPod Measurement
Body composition will be measured using a BodPod at study entry, 3 months after study entry, and 6 months after study entry.
• Liver Ultrasound
A liver ultrasound will be performed at study entry and 6 months after study entry.

Locations

Country	Name	City	State
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù 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. Epub 2006 Oct 5. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alterations in the intestinal microbiome are associated with increased immune activation and progression of obesity associated NAFLD.		3 years	No
Secondary	Characterize the intestinal microbiome through quantitative analysis of stool samples in participants with obesity and those with obesity and NAFLD.		3 years	No
Secondary	Characterize inflammatory markers of participants with obesity versus those obese participants that also have NAFLD.		3 years	No