Ketotifen in Non-Alcoholic Fatty Liver Disease Patients

Sponsor

Tanta University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05616442

Collaborator

(none)

Enrollment

Arms

12.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatic Disease	Drug: Ketotifen Drug: Vitamin E	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Ketotifen in Non-Alcoholic Fatty Liver Disease Patients

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 as Vitamine E group Vitamin E as standard therapy	Drug: Vitamin E Dietary supplement
Experimental: Group two as Ketotifen group Ketotifen as interventional	Drug: Ketotifen Mast cell stabilizer

Arm

Intervention/Treatment

Experimental: Group 1 as Vitamine E group

Vitamin E as standard therapy

Drug: Vitamin E

Dietary supplement

Experimental: Group two as Ketotifen group

Ketotifen as interventional

Drug: Ketotifen

Mast cell stabilizer

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

improvement of inflammatory biochemical markers as TNF [up to 6 months]
tumor necrosis factor measured by ELISA

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

-Inclusion criteria: Adult males or females aged ≥18 years.

All patients are diagnosed to have fatty liver grading 1, 2 or 3 on abdominal ultrasound with Hepatic steatosis index > 36 to be considered as a NAFLD patient.
Confirmed diagnosis of NASH
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.