Clinical trial NCT05284448: Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis
Official title: Effectiveness and Safety of Pentoxifylline in Treatment of Patients With Nonalcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: NASH - Nonalcoholic Steatohepatitis
Lead sponsor: Al-Azhar University
Sponsor class: OTHER
First posted: 2022-03-17
Enrollment: 50
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: Clinical trial, parallel, randomized, prospective, controlled study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: improvement in liver aminotransferases(ALT and AST)
timeFrame: 6 months compared to the baseline
measure: NAFLD fibrosis score (NFS)
timeFrame: 6 months compared to the baseline
Secondary outcomes:
measure: The Aspartate (AST) to Platelet Ratio Index (APRI) score:
timeFrame: 6 months compared to the baseline
measure: The Fibrosis-4 (FIB-4) values:
timeFrame: 6 months compared to the baseline
measure: Serum Alkaline Phosphatase level (ALP)
timeFrame: 6 months compared to the baseline
measure: Serum Gamma-glutamyl Transferase level (GGT)
timeFrame: 6 months compared to the baseline
measure: Serum total and direct bilirubin.
timeFrame: 6 months compared to the baseline
measure: Waist circumference
timeFrame: 6 months compared to the baseline
measure: Change in anthropometric measures
timeFrame: 6 months compared to the baseline
measure: Lipid profile
timeFrame: 6 months compared to the baseline
measure: Glycated hemoglobin (HbA1C)
timeFrame: 6 months compared to the baseline
measure: Fasting blood glucose level
timeFrame: 6 months compared to the baseline
measure: Drugs adverse events
timeFrame: 6 months compared to the baseline
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Internal medicine and hepatology outpatient clinic at Ain Shams University Hospital.
Study officials:
affiliation: Professor and Head of Clinical Pharmacy Department, Faculty of Pharmacy, Al-Azhar University(Girls, Cairo)
name: Zeinab Zalat, PhD
role: STUDY_CHAIR
affiliation: Assistant Professor of Pharmacology and Toxicology, Al-Azhar University (Boys, Assiut)
name: Adel Gaber Bakr, PhD
role: STUDY_DIRECTOR
affiliation: Assistant Professor of Internal Medicine and Gastroenterology, Faculty of Medicine, Ain-Shams University
name: Ahmed ElGhandour, MD
role: STUDY_DIRECTOR
affiliation: Demonstrator of Clinical Pharmacy Department, Faculty of Pharmacy, Al-Azhar University (Boys, Assiut)
name: ahmed abomandour, Demonstrator
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Girolami A. Tentative and updated classification of factor X variants. Acta Haematol. 1986;75(1):58-9. doi: 10.1159/000206084. No abstract available.