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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Vitamin E
* Drug: Ursodeoxycholic acid
* Drug: Pentoxifylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: Patients were ruled out if they had history of alcohol dependence treatment with drugs known to induce NASH (e.g. amiodarone, calcium channel blocker, tamoxifen, oral anticoagulation, methotrexate , steroids and estrogen) positive serologic markers for known chronic liver diseases (hepatitis B surface antigen, anti-hepatitis C virus antibody antinuclear antibody) human immunodeficiency virus (HIV) infection Diabetes decompensated liver disease defined as serum bilirubin level >1 mg/dL, albumin level ˂3.5 g/dL, and international normalized ratio (INR) ≥1.7.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective, randomized, and single blind study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group1<br>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<br>* Vitamin E is one of the body's most effective chain-breaking antioxidants that has shown to delay the pathogenesis of NASH.<br>* Other names: Alpha-Tocopherol;|
| Active Comparator: Group2<br>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<br>* 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)<br>* Other names: Ursofalk;|
| Active Comparator: Group3<br>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<br>* 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<br>* Other names: Trental;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin E, Ursodeoxycholic acid, Pentoxifylline, NASH