Comparative Study Between Obeticholic Acid Versus Vitamin E in Patients with Non-alcoholic Steatohepatitis

NCT05573204 | Active Not Recruiting Phase 2

• 1 other identifier: 34512/2/21
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at evaluating and comparing the protective outcomes of using Obeticholic acid versus Vitamin E in NASH patients without cirrhosis. The intervention is 6-months duration and the study will assess the efficacy of either drug as fibrosis improvement (≥ 1 stage) with no worsening of NASH or NASH resolution with no worsening of fibrosis with the study considered successful if either 1ry end point is met. . Also, assessment of biochemical markers related to steatosis, inflammation, oxidative stress, insulin resistance and liver fibrosis will be done.

Conditions

Non-alcoholic Steatohepatitis

Keywords

NAFLD, non alcoholic fatty liver, fatty liver

Outcome Measures

Primary Outcomes (2)

• Change from baseline fibrosis stage at 6 months; fibrosis improvement (≥ 1 stage), with no worsening of steatosis, detected by fibroscan device

  Patients will undergo fibroscan testing prior to the initiation of the intervention and after 6 months of receiving the drug therapy to detect fibrosis improvement

  6 months

• Change from baseline steatosis stage at 6 months with no worsening of fibrosis detected by Fibroscan device

  Patients will undergo fibroscan testing prior to the initiation of the intervention and after 6 months of receiving the drug therapy to detect steatosis improvement

  6 months

Secondary Outcomes (5)

• Change in serum level of fibroblast growth factor-21(FGF-21)

  6 months

• Change in serum level of cytokeratin-18 (CK-18)

  6 months

• Change in serum level of Liver enzymes; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)

  6 months

• Change in HAIR SCORE

  6 MONTHS

• change in BMI

  6 months

Study Arms (2)

Group 1 obeticholic acid group

ACTIVE COMPARATOR

28 non alcoholic steatohepatitis patients receiving obeticholic acid 10 mg once daily for 6 months duration

Drug: Obeticholic Acid Oral Tablet

Group 2 vitamin E group

ACTIVE COMPARATOR

31 non alcoholic steatohepatitis patients receiving vitamin E 400 mg twice daily for 6 months duration

Drug: Vit E

Interventions

Obeticholic Acid Oral Tablet DRUG

Obeticholic acid used as 10 mg tablet once daily for 6 months

Also known as: Nashiliv 10 mg

Group 1 obeticholic acid group

Vit E DRUG

Vitamin E used as 400 mg soft gelatin capsules twice daily for 6 months

Also known as: Vitamin E 400 mg

Group 2 vitamin E group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged ≥18 years.
• All patients are diagnosed to have fatty liver grading 1, 2 or 3 on abdominal ultrasound with Hepatic steatosis index \> 36 to be considered as a NAFLD patient.
• Confirmed diagnosis of NASH using at least three of the following non-invasive tests:
• HAIR score
• Fibroscan detecting steatosis with F0-3 fibrosis stage
• Cytokeratin-18 \>240 U/L
• Mild to moderate elevation of serum aminotransferases (\>2 but \<5 times upper normal limit)

You may not qualify if:

• Current or history of significant alcohol consumption.
• Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins).
• Prior or planned bariatric surgery.
• Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher.
• Evidence of other forms of chronic liver disease as Hepatitis B, Hepatitis C, Wilson's disease, Alpha-1-antitrypsin(A1AT) deficiency, Hemochromatosis, drug-induced liver disease.
• Serum creatinine of 2.0 mg/dL or greater.
• Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial and breast feeding.
• Use of other drugs known to have possible positive effects on steatosis.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine,Tanta University

Tanta, Egypt

Location

Related Publications (4)

• Venetsanaki V, Karabouta Z, Polyzos SA. Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis. Eur J Pharmacol. 2019 Nov 15;863:172661. doi: 10.1016/j.ejphar.2019.172661. Epub 2019 Sep 16.

  PMID: 31536725 BACKGROUND

• Yang ZX, Shen W, Sun H. Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease. Hepatol Int. 2010 Aug 12;4(4):741-8. doi: 10.1007/s12072-010-9202-6.

  PMID: 21286345 BACKGROUND

• Fuchs M. Non-alcoholic Fatty liver disease: the bile Acid-activated farnesoid x receptor as an emerging treatment target. J Lipids. 2012;2012:934396. doi: 10.1155/2012/934396. Epub 2011 Dec 7.

  PMID: 22187656 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.

  PMID: 28714183 BACKGROUND

Related Links

• Obeticholic action; all you need to know

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

obeticholic acid; Vitamin E

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hadier m. El-sheikh

  Department of Clinical pharmacy, Faculty of Pharmacy, Tanta university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer of clinical pharmacy- Clinical pharmacy department- Faculty of pharmacy

Model Details: This study is randomized controlled, parallel and prospective 6-months duration study. Accepted patients will be randomized into 2 groups as the following: * Group 1 (Obeticholic acid group): 30 patients will receive 10 mg/day OCA for 6 months. * Group 2 (Control group): 30 patients will receive Vitamin E 400 mg twice daily for 6 months.

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 10, 2022
• Study Start: September 1, 2021
• Primary Completion (Estimated): October 25, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 10, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)