Ketotifen in Non-Alcoholic Fatty Liver Disease Patients

Phase 4

Not yet recruiting

• Conditions: Hepatic Disease
• Interventions: Drug: Vitamin E; Drug: Ketotifen

• Registration Number: NCT05616442
• Lead Sponsor: Tanta University

Brief Summary

The aim of this study is to investigate the safety and efficacy of using ketotifen in patients with NAFLD patients without cirrhosis

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation and deposition of fats in the hepatocytes which affect the liver structure and function. Causes of NAFLD vary but mainly attributed to dyslipidemia and obesity. Prevalence of NAFLD has been raised over years from 25% in 2005 to over 37% in 2016 and continues to increase to become one of the most common chronic liver disease (Li J et al., 2019).

The disease progress from steatosis and inflammatory infiltration that is known as nonalcoholic steatohepatitis (NASH) to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Despite these serious outcomes, no definitive known approved medication for NASH has been developed. NAFLD management is mainly dependent on diet control, physical activity, and some supportive treatments mainly to prevent the disease complications (Mundi et al., 2020).

Mast cells (MCs) are responsible releasing mediators, including preformed bioactive metabolites (histamine and tryptase,), newly synthesized cytokines \[transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α) (Pham et al., 2022). MCs can lead to microvesicular steatosis, ductal reaction (DR), biliary senescence, inflammation, angiogenesis, and liver fibrosis during NAFLD/NASH (Huang et al., 2022). Consequently, MC stabilizer such as ketotifen has emerged as promising approach to improve patients with NASH through its antioxidant and anti-inflammatory effects (Kim et al., 2014; Abdelzaher et al., 2020).

Study Timeline

• Status Verified: 2022-11
• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-13
• Last Update Submitted: 2022-11-13
• Study First Posted: 2022-11-15
• Last Update Posted: 2022-11-15
• Study Start: 2022-12-01
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

• Current or history of significant alcohol consumption.
• Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins).
• Prior or planned bariatric surgery.
• Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher.
• Evidence of other forms of chronic liver disease as Hepatitis B, Hepatitis C, Wilson's disease, Alpha-1-antitrypsin (A1AT) deficiency, Hemochromatosis, drug-induced liver disease.
• Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial and breast feeding.
• Use of other drugs known to have possible positive effects on steatosis.
• Other anti-histaminic, sedating agents (CNS depressants) and anticholinergic medications.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 as Vitamine E group	Vitamin E	Vitamin E as standard therapy
Group two as Ketotifen group	Ketotifen	Ketotifen as interventional

Primary Outcome Measures

Name	Time	Method
fibrosis improvement (≥ 1 stage)	up to 6 months	F0: no fibrosis F1: portal fibrosis without septa by fibroscan

Secondary Outcome Measures

Name	Time	Method
improvement of inflammatory biochemical markers as TNF	up to 6 months	tumor necrosis factor measured by ELISA