Digestive System Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Liver Cirrhosis

Carcinoma

Fibrosis

Liver Neoplasms

Carcinoma, Ductal

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Hematinics

All Drugs and Chemicals

Liver Extracts

Patients complete surveys over 10-15 minutes, and undergo blood testing, clinical evaluation, and fibroscan at baseline.

Clinical Evaluation

Laboratory Biomarker Analysis

Liver Ultrasonographic Elastography

Survey Administration

Jessica P Hwang

This clinical trial studies the use of surveys, blood testing, and fibroscan in screening for liver fibrosis and liver cirrhosis in new or existing patients of the HOPE clinic seeking usual clinical care. Fibroscan is an imaging procedure of the liver which uses a probe like an ultrasound. Information gathered from this study may help researchers learn more about how to prevent or find liver cancer in patients who are currently receiving care at the HOPE clinic. Early detection of liver cancer may improve survival.

PRIMARY OBJECTIVE:

I. To estimate the sensitivity of the modified Center for Disease Control (CDC) hepatitis survey in diagnosing chronic hepatitis B virus (HBV) among HOPE clinic patient.

SECONDARY OBJECTIVES:

I. To estimate the sensitivity of the modified CDC hepatitis survey in identifying chronic active hepatitis C virus (HCV) infection among HOPE clinic patients.

II. To estimate the sensitivity of fibrosis serum biomarkers, non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), and fatty liver index (FLI) in detecting fibrosis (fibroscan result \>= F2) among HOPE clinic patients with metabolic conditions.

III. To estimate the sensitivity of the Alcohol Use Disorder Identification Test Alcohol Consumption (AUDIT-C) in identifying fibrosis (fibroscan result \>= F2) among HOPE clinic patients.

IV. To estimate the sensitivity of the AUDIT-10 survey in identifying fibrosis (Fibroscan result \>= F2) among Hope Clinic patients who scored \>= 4 for men or \>= 3 for women on the AUDIT-C.

V. To estimate the specificity and accuracy of each of these risk factor screening tools in HOPE clinic patients.

VI. To estimate the prevalence of fibrosis and cirrhosis risk factors among HOPE clinic patients.

EXPLORATORY OBJECTIVES:

I. To explore factors associated with each fibrosis/cirrhosis risk factor. II. To investigate differential diagnostic accuracy of screening methods by fibrosis severity.

III. To evaluate the diagnostic performance of each dichotomized biomarker (NFS, FIB-4, and FLI) separately and assess biomarker optimal cutpoints for identifying fibrosis in the study population.

OUTLINE:

Patients complete surveys over 10-15 minutes, and undergo blood testing, clinical evaluation, and fibroscan at baseline.

After completion of study, patients are followed up at 3 months.

Surveys, Blood Testing, and Fibroscan in Screening for Liver Fibrosis and Liver Cirrhosis

Patient-Centered Liver Cancer Prevention in the Houston Community Screening for Predictors of Fibrosis and Cirrhosis

The presence of at least one risk factor for hepatitis B virus (HBV) on the screening questionnaire will indicate a positive (versus negative) screening for HBV infection.

Will assess positive anti-HCV test result AND either 1) detectable HCV ribonucleic acid, or 2) history of HCV infection and past anti-HCV treatment. Will estimate the prevalence and exact binomial 95% confidence intervals for each of the fibrosis and cirrhosis risk factors examined in this study. For each risk factor, we will first present a cross tabulation of the dichotomous screening test result by the dichotomous gold standard result. To evaluate the performance of each screening method, will calculate point estimates and 95% confidence intervals for the sensitivity, specificity, likelihood ratio, and diagnostic odds ratio.

Will estimate the prevalence and exact binomial 95% confidence intervals for each of the fibrosis and cirrhosis risk factors examined in this study. For each risk factor, we will first present a cross tabulation of the dichotomous screening test result by the dichotomous gold standard result. To evaluate the performance of each screening method, will calculate point estimates and 95% confidence intervals for the sensitivity, specificity, likelihood ratio, and diagnostic odds ratio.

Cancer Prevention Research Institute of Texas

M.D. Anderson Cancer Center

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

Patients receive OCA PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound during screening, EGD with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study.

Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound during screening, EGD with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study.

Biospecimen Collection

Undergo esophageal biopsy, brushings and gastric aspirate

Esophageal Biopsy

Esophagogastroduodenoscopy

Undergo liver ultrasound with elastography

Obeticholic Acid

Placebo Administration

Questionnaire Administration

Ajay Bansal

Dean E. Brenner

Dayna S. Early

Nicholas J. Shaheen

Joseph E. Willis

Amitabh Chak

Prashanthi Thota

Dean E Brenner

This phase II trial studies the effect of obeticholic acid in treating patients with Barrett's esophagus. Bile acids present in duodenogastroesophageal reflux contribute to neoplastic progression in Barrett's esophagus. Obeticholic acid has shown anti-cholestatic, anti-inflammatory and anti-fibrotic effects mediated by FXR activation. It down regulates bile acid availability and decreases proinflammatory cytokine production including IL-1β and TNFα in human enterocytes and immune cells. This chain of events reduces the bile acid exposure in esophagus tissue thereby limiting bile acid induced damage and dysplastic progression.

PRIMARY OBJECTIVE:

I. To assess the mean change from baseline in the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) + cells in the crypts of esophageal tissue among patients with Barrett's esophagus (BE) receiving 25 mg of obeticholic acid (OCA), once daily from 0 to 180 days as compared to placebo.

EXPLORATORY OBJECTIVES:

I. To determine OCA concentrations and concentrations of the two major active metabolites, taurine, and glycine conjugates, in plasma after dosing with OCA 25 mg to determine the concentrations reached.

II. To assess the effects of treatment with OCA versus placebo on total and individual bile acid composition in Barrett's tissue, gastric aspirate, and serum.

III. To assess the effects of treatment with OCA versus placebo on serum levels of 7alpha-hydroxy-4- cholesten-3-one (C4), a key precursor in bile acid synthesis, and fibroblast growth factor-19 (FGF-19), a fibroblast growth factor which downregulates bile acid synthesis.

IV. To assess the effect of OCA on FXR expression in Barrett's tissue. V. To assess the effects of treatment with OCA versus placebo on biomarkers of the carcinogenic process - proliferation (Ki-67), apoptosis (cleaved caspase 3), and oxidative damage (8-hydroxydeoxyguanosine) as determined from Barrett's mucosal biopsies.

VI. To assess the effects of treatment with OCA versus placebo on histologic changes in Barrett's samples pre and post-intervention for development/ resolution of dysplasia.

VII. To assess the effects of treatment with OCA versus placebo on markers of differentiation- CDX2/SOX2/p53 expression in Barrett's tissue.

VIII. To assess the safety profile of treatment with OCA versus placebo which includes incidence and severity of pruritus and changes in serum total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and triglycerides.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive OCA orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Patients undergo liver ultrasound with elastography during screening, esophagogastroduodenoscopy (EGD) with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study.

After completion of the study treatment, patients are followed at 14-21 days.

The study statistician will be blinded towards the group's identity while analyzing the data. Further, neither the participants, nor the investigators will have any knowledge of the individual arm assignment.

Obeticholic Acid for Prevention in Barrett's Esophagus

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

These experiments will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using a specific, sensitive and reliable tandem mass spectrometry (ultraperformance liquid chromatography- tandem mass spectrometry \[UPLC-MS/MS\]) method. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is linear mixed models (LMM) with time, group, and time-by-group interaction as primary covariates.

These experiments will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using a specific, sensitive and reliable UPLC-MS/MS method to quantify the bile acid and conjugated metabolite concentration in human plasma and tissue samples. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

This experiment will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using UPLC-MS/MS. The blood based markers will be analyzed using a linear mixed model with study group as the primary between-subjects factor, and time (3-levels) along with the group-by-time interaction as the primary within-subjects factor. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

FGF19 concentrations will be assayed using the solid-phase enzyme-linked immunoabsorbant assay Quantikine FGF19 Immunoassay (R\&D Systems, Minneapolis, Minnesota) in the Immunology Core facility at the University of Michigan Rogel Cancer Center. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Performed by enzyme-linked immunosorbent assay. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Will include markers in proliferation (Ki-67), apoptosis (cleaved caspase 3), oxidative damage (8-hydroxydeoxyguanosine), glandular differentiation - CDX2/SOX2 as well as baseline p53 staining performed by multiplex immunofluorescence. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Performed in the Molecular Pathology Core Resource at University of Michigan Rogel Cancer Center. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Includes incidence and severity of pruritus and changes in serum total cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein and triglycerides. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

The mean difference in this percentage is compared across the two study arms by means of a two-sample t-test. As a further sensitivity analysis, the outcome of change will be analyzed under a linear regression model framework, controlling for factors such as age, gender, body mass index, and grade of dysplasia.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Surveys, Blood Testing, and Fibroscan in Screening for Liver Fibrosis and Liver Cirrhosis	NCT04785534	Liver and Intra...	Clinical Evalua... Laboratory Biom... Liver Ultrasono... Survey Administ...	18 Years -	M.D. Anderson Cancer Center
Obeticholic Acid for Prevention in Barrett's Esophagus	NCT04939051	Barrett Esophag...	Biospecimen Col... Esophageal Biop... Esophagogastrod... Liver Ultrasono... Obeticholic Aci... Placebo Adminis... Questionnaire A...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for liver ultrasonographic elastography