Microbiome-Mediated Gut Dysfunction in Non-Alcoholic Fatty Liver Disease

NCT05209100 | Active Not Recruiting

• 1 other identifier: 1584959
• Study Type: observational
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to generate the first human evidence to date on microbiota encroachment in non-alcoholic fatty liver disease. In parallel, the investigators will establish a biobank that will allow future studies to reveal how encroachment is connected to host metabolism and liver physiology, including the composition and function of the fecal microbiome.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

Microbiome, steatosis, fibrosis, obesity

Outcome Measures

Primary Outcomes (1)

• Microbiome Encroachment

  Measured via a combination of in situ hybridization and confocal microscopy to measure the distance of microbes from intestinal epithelial cells

  Baseline

Study Arms (3)

Normal Liver

Individuals will have no evidence of steatosis or fibrosis.

Procedure: Sigmoidoscopy

Steatosis Only

Individuals will have at least 5.6% liver fat as assessed by magnetic resonance imaging proton density fat fraction with no evidence of fibrosis as evidenced by magnetic resonance elastography.

Procedure: Sigmoidoscopy

Fibrosis without Cirrhosis

Individuals will have any level of liver fat as assessed by magnetic resonance imaging proton density fat fraction with fibrosis up to level F3 as evidenced by magnetic resonance elastography.

Procedure: Sigmoidoscopy

Interventions

Sigmoidoscopy PROCEDURE

During the sigmoidoscopy, biopsy tissue will be obtained for research purposes. Biopsies will be performed based on typical standard of care procedures without an antecedent bowel prep.

Fibrosis without Cirrhosis; Normal Liver; Steatosis Only

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals will be age 35-65, obese (BMI 27.5-39.9 kg/m2), and weight stable. Age is a microbiome modifier, particularly beyond age 65. This is why our upper age limit is 65. Young individuals are also less likely to have NAFLD, thus our starting age is 35. The investigators will exclude individuals with a history of other forms of liver disease, bariatric surgery, or other relevant contraindications to participation.

You may qualify if:

• Age 35-65 years
• Weight stable (weight change of no more than 3 kg + 0.5 kg) during the 6 months prior to enrollment
• Fasting triglycerides ≤400 mg/dL
• Body mass index (BMI) 27.5-39.9 kg/m2
• Able to speak and understand written and spoken English
• Understands the procedures and agrees to participate by giving written informed consent
• Willing and able to comply with scheduled visits, laboratory tests, and other study procedures
• Magnetic Resonance Imaging Proton Density Fat Fraction Criteria:
• Controls: \<5%
• Steatosis Only: ≥5.6%
• Fibrosis: no specific percentage required
• Magnetic Resonance Elastography Criteria:
• Controls: \< 2.50 kPa
• Steatosis Only: \<2.50 kPa
• Fibrosis (without cirrhosis): \>2.61 - \< 4.69 kPa

You may not qualify if:

• Acute or chronic medical conditions or medication that would contraindicate the participation in the research testing or could potentially affect metabolic function including, but not limited to:
• Diagnosis of type 1 or type 2 diabetes mellitus
• Insulin use
• Treatment with pioglitazone or metformin
• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within the previous 6 months (1 drink = 5 ounces \[150 mL\] of wine, 12 ounces \[360 mL\] of beer, or 1.5 ounces \[45 mL\] of hard liquor)
• A total score of ≥8 on the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, indicating harmful or hazardous alcohol consumption
• Clinical evidence of hepatic decompensation, including, but not limited to esophageal varices, ascites, or hepatic encephalopathy.
• Evidence of other forms of chronic liver disease (including laboratory tests and confirmed with a single repeat, if needed):
• Hepatitis B virus: defined by presence of hepatitis B surface antigen
• Hepatitis C virus: As defined by a clinical history of previous diagnosis of Hepatitis C (treated or untreated) or a positive Hepatitis C antibody.
• Known diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome
• Alcoholic liver disease
• Known diagnosis of hemochromatosis
• Prior known drug-induced liver injury
• Known or suspected hepatocellular carcinoma or other liver cancer

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

AdventHealth Translational Research Institute

Orlando, Florida, 32804, United States

Location

Related Links

• AdventHealth Translational Research Institute

Biospecimen

Retention: SAMPLES WITH DNA

Both human and microbial DNA

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver; Fibrosis; Obesity

Interventions

Sigmoidoscopy

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colonoscopy; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Karen Corbin, PhD, RD

  Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 26, 2022
• Study Start: February 11, 2022
• Primary Completion: March 22, 2023
• Study Completion: December 1, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Locations

US (1)