Clinical trial NCT04977661: Comparing the Effects of Vitamin E, Ursodeoxycholic Acid and Pentoxyfylline on Egyptian Non-alcoholic Steatohepatitis (NASH) Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: Vitamin E, Ursodeoxycholic acid, Pentoxifylline, NASH
Lead sponsor: Kafrelsheikh University
Sponsor class: OTHER
First posted: 2021-07-27
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, and single blind study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Resolution of NASH
timeFrame: 3 months
Secondary outcomes:
measure: Normalization of hepatic aminotransferases(ALT and AST)
timeFrame: 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Hepatology, gastroenterology and infectious diseases department at Kafrelsheikh University Hospital
Study officials:
References:
citation: 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.