Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis

Phase 3

Completed

• Conditions: NASH - Nonalcoholic Steatohepatitis
• Interventions: Drug: pentoxifylline (Trental SR®)

• Registration Number: NCT05284448
• Lead Sponsor: Al-Azhar University

Brief Summary

The aim of the present study is to evaluate the efficacy and safety of pentoxifylline in the treatment of non-alcoholic steatohepatitis patients.

Detailed Description

Nonalcoholic steatohepatitis(NASH) is the progressive form of Non-alcoholic fatty liver disease (NAFLD), is characterized by hepatocellular damage, inflammation, and liver fibrosis that can progress to cirrhosis, in 25% of patients, NAFLD progresses to NASH, which increases the risk for the development of cirrhosis, liver failure, and hepatocellular carcinoma. In patients with NASH, liver fibrosis is the main determinant of mortality.

Pentoxifylline (PTX) is a xanthine derivative drug with a wide range of actions at the cellular and molecular level. PTX possess anti-inflammatory, antioxidant activities. PTX have potential role in improvement of NASH . Also, PTX inhibits a number of pro-inflammatory cytokines including interleukin-1, interleukin-6 and tumor necrosis factor (TNF-α ) which play an important role in the pathogenesis and progression of NASH.

Study Timeline

• Study Start: 2022-02-01
• Study First Submitted: 2022-02-16
• Study First Submitted QC: 2022-03-09
• Study First Posted: 2022-03-17
• Primary Completion: 2022-09-01
• Study Completion: 2022-10-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Aged between 18- 60 years old.

2. Both sexes

3. Patients who have nonalcoholic steatohepatitis (NASH) will be diagnosed by

   1. clinical examination (obese, high body mass index).
   2. radiological criteria of fatty liver (abdominal ultrasonography).
   3. laboratory investigation (elevated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT).

4. The ability to give informed consent

5. Appropriate exclusion of other liver diseases

Exclusion Criteria

1- Patients with other diagnosed chronic liver diseases as viral hepatitis, metabolic and genetic disorders as Hemochromatosis, Wilson disease, autoimmune hepatitis and drug induced liver disease as well as patients with recent infection and those who refused to be entitled in the study.

2. Patients will be excluded if they had a history of past excessive alcohol drinking for a period longer than 2 years at any time in the past 10 years.

3. Patients also will be excluded if they take medications known to cause steatosis or taking medications that have shown benefits in previous NASH pilot studies, including vitamin E, , thiazolidinedione, and alpha-glucosidase inhibitors.

4. Patients with a history of hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, and theobromine) will be excluded, as well as those with a history of cerebral

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pentoxifylline Group	pentoxifylline (Trental SR®)	25 patients will receive pentoxifylline (Trental SR®) 400 mg three times daily with their standard therapy for 6 months.

Primary Outcome Measures

Name	Time	Method
NAFLD fibrosis score (NFS)	6 months compared to the baseline	Change in NAFLD fibrosis score (NFS) (lower score means better outcome).
improvement in liver aminotransferases(ALT and AST)	6 months compared to the baseline	Difference between last and first measurements

Secondary Outcome Measures

Name	Time	Method
Waist circumference	6 months compared to the baseline	Change in waist circumference
Change in anthropometric measures	6 months compared to the baseline	including BMI etc.
Drugs adverse events	6 months compared to the baseline	Assessment of safety by reporting any adverse events
Serum Gamma-glutamyl Transferase level (GGT)	6 months compared to the baseline	Change in GGT serum level as inflammatory markers of NASH
Fasting blood glucose level	6 months compared to the baseline	Change in fasting blood glucose for patients with T2DM
The Aspartate (AST) to Platelet Ratio Index (APRI) score:	6 months compared to the baseline	Change in (APRI) score (lower score means better outcome).
The Fibrosis-4 (FIB-4) values:	6 months compared to the baseline	Change in (FIB-4) values (lower values means better outcome).
Serum total and direct bilirubin.	6 months compared to the baseline	Change in levels of serum total and direct bilirubin.
Lipid profile	6 months compared to the baseline	Change in serum lipids
Glycated hemoglobin (HbA1C)	6 months compared to the baseline	Change in HbA1C level for patients with T2DM
Serum Alkaline Phosphatase level (ALP)	6 months compared to the baseline	Change in ALP serum level as inflammatory markers of NASH

Trial Locations

Locations (1)

Internal medicine and hepatology outpatient clinic at Ain Shams University Hospital.; 🇪🇬 Cairo, Egypt