Comparing the Effects of Vitamin E, Ursodeoxycholic Acid and Pentoxyfylline on Egyptian Non-alcoholic Steatohepatitis (NASH) Patients

A Randomized Study to Compare the Efficacy of Vitamin E, Ursodeoxycholic Acid and Pentoxyfylline on Egyptian Patients With Non-alcoholic Fatty Liver Disease Using (IL6 and CCL2) as a Predictors of Non-alcoholic Steatohepatitis

We conducted a 3-month, randomized, single-blind study in 102 Egyptian NASH patients who were divided into three groups; group 1 included 34 patients received Vit. E 400 mg twice a day, group 2 included 34 patients received UDCA 250 mg twice a day and group 3 included 34 patients received PTX 400 mg twice daily for 3 months. The following parameters were measured both before and after intervention intake; liver aminotransferases (AST, ALT), cytokine and chemokine (IL6 and CCL2/MPC-1), albumin, total bilirubin, direct bilirubin, total cholesterol, triglyceride, LDL, HDL.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Vitamin E; Drug: Ursodeoxycholic acid; Drug: Pentoxifylline

Detailed Description

This was a 3-month, prospective, randomized, and single blind study. Participants were recruited from the outpatient clinic and hepatology, gastroenterology and infectious diseases department at Kafrelsheikh University Hospital between February 2020 and January 2021. Two-hundred and five Egyptian patients diagnosed with NAFLD with potential clinical inclusion criteria were invited for a screening session to determine their eligibility for the study. Patients were enrolled in the study if they are > 18 years old, had evidence for NASH; persistently elevated alanine aminotransferase (ALT) >1.5 times the upper limit of normal), imaging (ultrasound) showing fatty infiltration, and histological evidence of NASH after biopsy (macrovascular steatosis, ballooning degeneration of hepatocytes, scattered lobular inflammation and apoptotic bodies).One hundred and forty-six patients were excluded from the study either because they did not meet the inclusion criteria (n = 135) or refused to enroll in the study (n =11). Qualifying participants (n = 102) were randomly assigned to one of the three treatment groups using a computer-generated randomization sequence. Group I (n = 34) received 400 IU Vitamin E (Vitamin E 400 IU®, MEPACO Pharmaceutical Company, Sharqia, Egypt) twice daily for 3 months. Group II (n =34) received 250 mg Ursodeoxycholic acid (Ursofalk 250 mg®, MINAPHARM Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months. Group III (n = 34) received 400 mg sustained release (SR) Film-Coated Tablets of pentoxifylline (Trental 400 mg®, SANOFI Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months. Patients were followed up every week to ensure compliance, drug adherence and to report side effects or drop out from the study.The following parameters were measured both before and after intervention intake; liver aminotransferases (AST, ALT), cytokine and chemokine (IL6 and CCL2/MPC-1), albumin, total bilirubin, direct bilirubin, total cholesterol, triglyceride, LDL, HDL.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 33511
    • Hepatology, gastroenterology and infectious diseases department at Kafrelsheikh University Hospital

Participation Criteria

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:

• Patients were enrolled in the study

  1. if they are > 18 years old
  2. had evidence for NASH; persistently elevated alanine aminotransferase (ALT) >1.5 times the upper limit of normal)
  3. imaging (ultrasound) showing fatty infiltration, and histological evidence of NASH after biopsy (macrovascular steatosis, ballooning degeneration of hepatocytes, scattered lobular inflammation and apoptotic bodies).

Exclusion Criteria:

• Patients were ruled out if they had

  1. history of alcohol dependence
  2. treatment with drugs known to induce NASH (e.g. amiodarone, calcium channel blocker, tamoxifen, oral anticoagulation, methotrexate , steroids and estrogen)
  3. positive serologic markers for known chronic liver diseases (hepatitis B surface antigen, anti-hepatitis C virus antibody antinuclear antibody)
  4. human immunodeficiency virus (HIV) infection
  5. Diabetes
  6. decompensated liver disease defined as serum bilirubin level >1 mg/dL, albumin level ˂3.5 g/dL, and international normalized ratio (INR) ≥1.7.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group1; Group I (n = 34) received 400 IU Vitamin E (Vitamin E 400 IU®, MEPACO Pharmaceutical Company, Sharqia, Egypt) twice daily for 3 month	Drug: Vitamin E; Vitamin E is one of the body's most effective chain-breaking antioxidants that has shown to delay the pathogenesis of NASH.; Other Names: Alpha-Tocopherol
Active Comparator: Group2; Group II (n =34) received 250 mg Ursodeoxycholic acid (Ursofalk 250 mg®, MINAPHARM Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months	Drug: Ursodeoxycholic acid; is a metabolic by-product of intestinal bacteria and has been proven to be useful in the non-surgical treatment of cholesterol gallstones and primary biliary cirrhosis (PBC); Other Names: Ursofalk
Active Comparator: Group3; Group III (n = 34) received 400 mg sustained release (SR) Film-Coated Tablets of pentoxifylline (Trental 400 mg®, SANOFI Pharmaceutical Company, Cairo, Egypt) twice daily for 3 months	Drug: Pentoxifylline; it is a well-tolerated medication that improves blood viscosity and erythrocyte rheological characteristics in individuals with peripheral vascular disease 20. In addition, PTX is a nonspecific phosphodiesterase inhibitor that increases cyclic adenosine monophosphate (cAMP) levels while decreasing TNF-a gene transcription; Other Names: Trental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of NASH	Relieve clinical symptoms and prevent progression	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of hepatic aminotransferases(ALT and AST)	ALT and AST return to normal values	3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University

Publications and helpful links

General Publications

• Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, Wai-Sun Wong V, Yilmaz Y, George J, Fan J, Vos MB. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. 2019 Jun;69(6):2672-2682. doi: 10.1002/hep.30251.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): May 20, 2020
• Study Completion (Actual): January 10, 2021

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin E, Ursodeoxycholic acid, Pentoxifylline, NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Gastrointestinal Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Cholagogues and Choleretics; Vitamin E; Tocopherols; alpha-Tocopherol; Ursodeoxycholic Acid; Pentoxifylline
• Other Study ID Numbers: 154569224578

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No