Ignite Creation Date:
2025-12-24 @ 7:09 PM
Ignite Modification Date:
2025-12-27 @ 12:16 PM
Study NCT ID:
NCT06113003
Status:
RECRUITING
Last Update Posted:
2025-07-08
First Post:
2023-10-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Gut, Liver And Metabolome in Human Immunodeficiency Virus and Non Alcoholic Fatty Liver Disease
Sponsor:
Vanderbilt University Medical Center
Organization:
Study Overview
Official Title:
The Gut, Liver And Metabolome in Human Immunodeficiency Virus and Non Alcoholic Fatty Liver Disease
Status:
RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GLAM HIV NAFLD
Brief Summary:
Persons with human immunodeficiency virus (HIV) have higher risk of developing fatty liver disease (NAFLD) than HIV-negative persons but the reasons for this discrepancy are not known. Changes in the intestinal microbiome may contribute to the development of NAFLD in persons with HIV (PWH) through impairment of barrier function of the intestinal wall and by producing metabolites that are harmful to the liver. This project will test the hypothesis that HIV-related NAFLD is associated with differences in the intestinal microbiome and that supplementation with probiotic and prebiotic fiber will lead to improvements in markers of NAFLD in PWH.
Detailed Description:
Over 1.1 million people in the United States are living with human immunodeficiency virus (HIV). Liver disease is a leading cause of mortality in persons with HIV (PWH), and PWH suffer a disproportionate burden of non-alcoholic fatty liver disease (NAFLD). While the mechanisms underlying this disparity are not well understood, harmful changes in the intestinal microbiome ("dysbiosis") and increased bacterial product movement across the intestinal lining ("leaky gut") are implicated in the pathogenesis of NAFLD in HIV-negative persons. HIV infection has been shown to alter the intestinal microbiome and promote leaky gut; however, there are few data on the microbiome among PWH with NAFLD. Our overarching hypothesis is that intestinal dysbiosis in PWH promotes NAFLD through: 1) impairment of the barrier function of the intestinal lining causing translocation of proinflammatory bacterial products to the bloodstream and 2) alteration of plasma metabolites that promote NAFLD. Specifically, HIV-associated gut dysbiosis leads to reduction in the production of short chain fatty acids, which are essential for the maintenance of a healthy intestinal lining. A reduction in butyrate production leads to breakdown of the intestinal barrier, allowing for translocation of inflammatory bacterial products into the splanchnic vasculature and the liver. These products lead to inflammation and disruption of lipid metabolism in the liver causing lipid deposition in the liver. Additionally, dysbiosis in PWH leads to lower bacterial production of lipids necessary for fat metabolism in the liver leading to NAFLD. We will test these hypotheses in a single arm pre/post feasibility and efficacy trial of an intervention designed to restore a healthy gut microbiome in PWH with NAFLD (n=63). The study will assess the effects of a probiotic containing multiple strains of bacteria supporting butyrate synthesis and prebiotic fiber among PWH at risk of NAFLD (diagnosis of metabolic syndrome, elevated BMI or elevated transaminases) without history of current excessive alcohol use, viral hepatitis or other known liver diseases.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: