Fecal Microbiota Analysis of PNPLA3 Polymorphism in Hispanic Patients With MASLD

NCT06495333 | Recruiting

• 1 other identifier: FDI-2024-001
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common cause of liver disease worldwide. The condition is defined by fat accumulation exceeding 5% of liver weight not explained by at-risk alcohol intake. Risk factors include obesity, diabetes, genetic variants, dietary factors, and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unclear. The investigators aim to investigate the changes in the gut microbiome of Hispanics living in Puerto Rico with MASLD associated with wild-type and mutated genotype status of PNPLA3 rs738409, a strong genetic contributor to MASLD. In this cross-sectional study, blood and fecal samples will be collected from participants who have completed a non-invasive transient elastography test (FibroScan) to measure the extent of hepatic steatosis (fat in the liver). Genotyping for the PNPLA3 rs738409 variant will be conducted. Fecal samples will be collected to analyze the V4 region of the 16S rRNA gene for intestinal microbiota characterization. Alpha and beta diversity analysis will be measured by MASLD status and PNPLA3 genotype to evaluate biodiversity within and between samples.

Conditions

Metabolic Dysfunction-associated Steatotic Liver Disease

Keywords

MASLD; NAFLD

Outcome Measures

Primary Outcomes (2)

• Microbiota characterization

  To determine the changes in the gut microbiome of Hispanics living in Puerto Rico with MASLD associated to wild-type and mutated genotype status of PNPLA3 rs738409, a strong genetic contributor to MASLD.

  1 year

• Microbiota diversity based on eating patterns

  To determine microbiome diversity in Hispanics with different eating patterns.

  1 year

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The aim of this study is to determine the changes in the gut microbiome in Hispanics living in Puerto Rico with MASLD associated to wild-type and mutated PNPLA3 genotype status will also be assessed in this study population. To maintain homogeneity of the study population and to achieve the study objectives, the study will only be including individuals who self-identify as Hispanic and currently reside in Puerto Rico. Exclusion of non-Hispanic individuals is necessary to ensure that obtained results are representative of the Hispanic population in Puerto Rico and can be generalized to this population.

You may qualify if:

• Patient must be of Hispanic ethnicity residing in Puerto Rico. Age 21 to 75 years old at time of informed consent. Evidence of MASLD by vibration-controlled transient elastography (FibroScan) controlled attenuation parameter (CAP) (value must be greater than or equal to 248 dB/m).
• Willing and able to provide informed consent signed by study subject. Willing and able to understand and complete study-related procedures.

You may not qualify if:

• A subject who meets any of the following criteria will be excluded from the study:
• Excessive alcohol intake for ≥3 months during past year prior to screening (\>3 units/day for males and \>2 units/day for female is generally considered excessive).
• History of liver transplant, or current placement on a liver transplant list. History of viral and resolved hepatitis (Hepatitis B or C) or human immunodeficiency virus (HIV).
• Use of antibiotics within 14 days of screening.

Sponsors & Collaborators

• Fundacion de Investigacion Science and Education: lead

Study Sites (1)

FDI Clinical Research

San Juan, 00927, Puerto Rico

RECRUITING

Related Publications (6)

• Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012. Epub 2016 Jan 4.

  PMID: 26823198 BACKGROUND

• Chan WK, Chuah KH, Rajaram RB, Lim LL, Ratnasingam J, Vethakkan SR. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review. J Obes Metab Syndr. 2023 Sep 30;32(3):197-213. doi: 10.7570/jomes23052. Epub 2023 Sep 13.

  PMID: 37700494 BACKGROUND

• Godoy-Matos AF, Silva Junior WS, Valerio CM. NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020 Jul 14;12:60. doi: 10.1186/s13098-020-00570-y. eCollection 2020.

  PMID: 32684985 BACKGROUND

• Lang S, Martin A, Zhang X, Farowski F, Wisplinghoff H, J G T Vehreschild M, Krawczyk M, Nowag A, Kretzschmar A, Scholz C, Kasper P, Roderburg C, Mohr R, Lammert F, Tacke F, Schnabl B, Goeser T, Steffen HM, Demir M. Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease. Liver Int. 2021 Jul;41(7):1576-1591. doi: 10.1111/liv.14899. Epub 2021 May 7.

  PMID: 33896117 BACKGROUND

• Tilg H, Adolph TE, Moschen AR. Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade. Hepatology. 2021 Feb;73(2):833-842. doi: 10.1002/hep.31518. Epub 2021 Feb 6. No abstract available.

  PMID: 32780879 BACKGROUND

• Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008 Dec;40(12):1461-5. doi: 10.1038/ng.257. Epub 2008 Sep 25.

  PMID: 18820647 BACKGROUND

Related Links

• New MASLD Nomenclature
• Nonalcoholic Fatty Liver Disease (NAFLD)
• Fatty liver disease diet: What foods help prevent and reverse fatty liver?.
• Non-Alcoholic Fatty Liver Disease: Assessment and Management.

Biospecimen

Retention: SAMPLES WITH DNA

whole blood and fecal sample

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Andrea Pi, BS

  FDI Clinical Research

  STUDY CHAIR

Central Study Contacts

Vivian Tamayo, MD

CONTACT

787-722-1248; vtamayo@fdipr.com

Grisell Ortiz-Lasanta, MD

CONTACT

7877221248; gortiz@fdipr.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: July 10, 2024
• Study Start: July 5, 2024
• Primary Completion: December 28, 2024
• Study Completion: August 20, 2025
• Last Updated: July 10, 2024

Record last verified: 2024-07

Locations

PR (1)