Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis

Effectiveness and Safety of Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis

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

Study Overview

• Status: Active, not recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: pentoxifylline (Trental SR®)

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Internal medicine and hepatology outpatient clinic at Ain Shams 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:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pentoxifylline Group; 25 patients will receive pentoxifylline (Trental SR®) 400 mg three times daily with their standard therapy for 6 months.	Drug: pentoxifylline (Trental SR®); 400 mg three times daily
No Intervention: Control Group; 25 patients will receive their standard therapy only

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Al-Azhar University
• Investigators: Study Chair: Zeinab Zalat, PhD, Professor and Head of Clinical Pharmacy Department, Faculty of Pharmacy, Al-Azhar University(Girls, Cairo); Study Director: Adel Gaber Bakr, PhD, Assistant Professor of Pharmacology and Toxicology, Al-Azhar University (Boys, Assiut); Study Director: Ahmed ElGhandour, MD, Assistant Professor of Internal Medicine and Gastroenterology, Faculty of Medicine, Ain-Shams University; Principal Investigator: ahmed abomandour, Demonstrator, Demonstrator of Clinical Pharmacy Department, Faculty of Pharmacy, Al-Azhar University (Boys, Assiut)

Publications and helpful links

General Publications

• Leoncini L, Vindigni C, Megha T, Funto I, Pacenti L, Musaro M, Renieri A, Seri M, Anagnostopoulos J, Tosi P. Epstein-Barr virus and gastric cancer: data and unanswered questions. Int J Cancer. 1993 Apr 1;53(6):898-901. doi: 10.1002/ijc.2910530605.
• Girolami A. Tentative and updated classification of factor X variants. Acta Haematol. 1986;75(1):58-9. doi: 10.1159/000206084. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• 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; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 312 (CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No