Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT (NAFLD)

May 15, 2022 updated by: Md. Fazal Karim, Sir Salimullah Medical College Mitford Hospital

Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT- A Randomized Clinical Control Trial Study

This study will be conducted upon the patients with fatty liver disease. Patients who will be diagnosed as a case of fatty liver disease by ultrasound with raised liver enzyme (ALT) will be primarily selected for the study. A total number of 70 patients will be randomly selected for the study that will also be divided into two groups for the study purpose. The patients will be informed about the details of the study. After getting the detail information those who will give informed written consent will be finally included in the study. One group of patients will be treated by both life style modification and Obeticholic acid. Another group of patients by only life style modification. After 3 months of treatment the two groups will be compared of improvement of fatty liver disease and liver enzyme by improvement of fibroscan with CAP value as well as improvement of ALT value.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease worldwide and it is associated with increased liver-related mortality and hepatocellular carcinoma, even in the absence of cirrhosis. The prevalence of NAFLD is steadily increasing and is currently 20%-30% in Western countries and 5%-18% in Asia. It progresses to cirrhosis in 15-20% of affected individuals and is a rising indication for liver transplantation. NAFLD is the commonest cause of elevated liver enzymes. Lifestyle modifications, including diet and exercise, are imperative for achieving weight loss and reducing insulin resistance and hepatic steatosis and inflammation in patients with NAFLD. But are suboptimal by long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid, a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that obeticholic acid improves hepatic steatosis, inflammation and fibrosis. A randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received obeticholic acid. So, there is a need to develop more effective and safe agents for this common and life-threatening disease.

Farnesoid X receptor (FXR) is a member of the nuclear receptor super family expressed in the liver, kidney, intestine and adrenal glands. In addition to regulation of bile acid (BA) synthesis, several lines of evidence have suggested that FXR plays a role in the pathophysiology of NAFLD/NASH. Obeticholic acid is a synthetically modified bile acid that is a potent agonist of the farnesoid X nuclear receptor (FXR), a nuclear receptor with major effects on bile acid synthesis and transport as well as lipid metabolism and glucose homeostasis. Obeticholic acid has been shown to improve serum enzymes in several diseases including nonalcoholic fatty liver disease and primary biliary cirrhosis. In FLINT trial treatment with obeticholic acid (25 mg/day for 72 weeks) resulted in a highly statistically significant improvement in the NAFLD Activity Score of at least two points, with no worsening of fibrosis. 45% (50 of 110) of the treated group had this improvement compared with 21% (23 of 109) of the placebo-treated controls.

The objective of the study will be to assess the efficacy of obeticholic acid on improvement of NAFLD and ALT values in patients with fatty liver disease.

The study will be conducted in the department of Hepatology, Sir Salimullah Medical College and Mitford Hospital. It will be a randomized open label clinical control trial study. Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) will be initially targeted for the study. Patients who will be diagnosed as a case of NAFLD by ultrasound with raised Alanin aminotransferase (ALT) (>40 U/L) will be primarily selected for the study. The total sample size will be 70 that will be divided into two groups (Group-A and Group-B) for the study purpose. The patients will be informed about the details of the study. After getting the detail information, those who will give informed written consent will be finally included in the study. A series of baseline investigations including CBC with ESR, fasting blood sugar (FBS), 2 hours after 75 g glucose, alanine aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), bilirubin (B), PT with INR, serum albumin, total cholesterol (TC) & triglycerides (TG), LDL-C, HDL-C, Thyroid function test will be determined on fresh serum using an auto-analyzer. Fibroscan with CAP as well as ALT will be done to assess the baseline status of the patients at the time of enrollment of the study. Group-A patients will be treated by both life style modification and Obeticholic acid and Group-B patients by only life style modification. We shall give 10 mg obeticholic acid twice daily to the patients of Group-1. Life style modification including moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day will be advised to all the patients in both Groups. The patients will be followed for 3 months. Patients will come for follow-up after 1 month and finally after 3 months. Each visit will take place between 10.00 am to 02.00 p.m. & consist with a clinical examination, blood pressure (BP) & body mass index (BMI) determinations and a questionnaire. BMI will be computed using the formula: [weight (kg)]/ [square of height (meters)]. Serum will be collected for CBC with ESR, FBS, 2 hours after 75 g glucose, ALT, AST, PT with INR, serum albumin, GGT, TC, TG, HDL, LDL in first and last visit. An alcohol consumption questionnaire will also be administered in each visit and study compliance will be strictly monitored. After 3 months of treatment the two groups will be compared of improvement of NAFLD and liver enzyme by improvement of fibroscan with CAP value as well as improvement of ALT value with the baseline ALT and fibroscan with CAP values.

All Data will be presented as mean ± SD & analyzed by SPSS (version 23). Qualitative data will be analyzed by Chi-square test & quantitative data will be analyzed by student's t-test. A statistically significant result will be considered when P value < 0.05.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh, 1000
        • Department of Hepatology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • NAFLD (by USG)
  • Raised ALT (>40 U/L)

Exclusion Criteria:

  • Patient with significant alcohol intake (more than 20 gm/day).
  • Patient with history of taking drugs that may cause fatty liver (i.e. tamoxifen, valproic acid, amiodarone, methotrexate, steroid, OCP) or history of taking drugs that have shown benefit in previous NASH pilot studies (i.e. vitamin E, metformin, thiazolidinediones, statin, ARB, fibrates, DPP-4 inhibitor, Omega-3 fatty acid).
  • Chronic viral hepatitis (HBV, HCV).
  • Pregnancy
  • Patient with co-morbid condition (COPD, CKD, CCF etc.)
  • Patient with history of recent MI
  • Patient with liver failure
  • Patient with hypothyroidism

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Obeticholic acid
Patients diagnosed as NAFLD with raised ALT will be treated with both life style modification and Obeticholic acid. Obeticholic acid will be given as 10 mg twice daily. Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.
Drug: Obeticholic acid
Farnesoid X receptor ligand which is a semi synthetic bile acid analogue
Other Names:
  • Life style modification
No Intervention: Lifestyle modification
Patients diagnosed as NAFLD with raised ALT will be given only life style modification.Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in fibroscan score (Kpa) and CAP value (Kpa) which signifies fibrosis and steatosis status respectively.
Time Frame: For 12 weeks from the date of enrollment of the patient.

Obeticholic acid and life style modification improve fibroscan with CAP results in patients with NAFLD.

  1. Change in symptoms after 12 weeks of treatment or life style modification.
  2. Change in liver function test, fibroscan values and CAP values after treatment or life style modification.
For 12 weeks from the date of enrollment of the patient.
Change in BMI (weight in kg/height in meter square)
Time Frame: For 12 weeks from the date of enrollment of the patient.
For 12 weeks from the date of enrollment of the patient.
Change in ALT (U/L)
Time Frame: For 12 weeks from the date of enrollment of the patient.
For 12 weeks from the date of enrollment of the patient.
Fasting blood sugar (FBS) (mmol/L)
Time Frame: For 12 weeks from the date of enrollment of the patient.
For 12 weeks from the date of enrollment of the patient.
2 hours after 75 gm glucose (mmol/L)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Serum bilirubin (mg/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Aspertate aminotransferase (AST) (U/L)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Gamma glutamyle transpeptidase (GGT) (U/L)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Serum albumin (gm/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Prothrombin time (PT) (sec)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Total cholesterol (mg/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
Triglyceride (TG) (mg/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
LDL cholesterol (mg/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient
HDL cholesterol (mg/dl)
Time Frame: For 12 weeks from the date of enrollment of the patient
For 12 weeks from the date of enrollment of the patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sir Salimullah Medical College Mitford Hospital

Investigators

  • Principal Investigator: Md F Karim, MBBS,FCPS,MD, Sir Salimullah Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2019

Primary Completion (Actual)

November 30, 2020

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

January 9, 2019

First Submitted That Met QC Criteria

February 8, 2019

First Posted (Actual)

February 11, 2019

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 15, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SirSalimullahMCMH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

After completion of the study and statistical analysis, the study report will be published

IPD Sharing Time Frame

February'2019-June'2019

IPD Sharing Access Criteria

drfazalkarim@gmail.com

IPD Sharing Supporting Information Type

  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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