The Leukotriene Receptor Antagonist Montelukast in the Treatment of Non-alcoholic Steatohepatitis

The Leukotriene Receptor Antagonist Montelukast in the Treatment of Non-alcoholic Steatohepatitis: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

The aim of the current study is to evaluate the safety and efficay of Montelukast in treatment of patients with fatty liver disease.

Study Overview

• Status: Completed
• Conditions: Steatohepatitis, Nonalcoholic
• Intervention / Treatment: Drug: Control group; Drug: Montelukast group

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Menoufia
    • Shibīn Al Kawm, Menoufia, Egypt, 13829
      • Faculty of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- The inclusion criteria were adult patients (age >18 years old) of both sexes, overweight/obese subjects with presence of evidence of hepatic steatosis by imaging (increased liver echogenicity, stronger echoes in the hepatic parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins). Patients with mild to moderate elevation in aminotransferase activities (> 2 but <5 times upper limit of normal), hepatic steatosis index (HIS) >36, Fibro-scan score >7 kpa and <12.5 kpa (F0-F3), and HAIR score of 2 or 3 were included in the study.

Exclusion Criteria:

- The exclusion criteria included smokers, patients with secondary hepatic fat accumulation which results from using steatogenic medications or hereditary disorders. Alcohol consumers, patients with Wilson's disease, hemochromatosis, viral hepatitis, decompensated liver disease, inflammatory diseases, diabetes, depression and patients with other comorbid conditions that elevate transaminases (congestive heart failure and malignancy) pregnancy and lactating women were excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; 26 patients will receive placebo (Control group)	Drug: Control group; patients received matching-image placebo once daily at bedtime for 12 weeks.
Experimental: Montelukast group; 26 patients will receive montelukast 10 mg/ day	Drug: Montelukast group; patients received montelukast (10-mg chewable tablet) once daily at bedtime for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibro-scan score	change in liver stiffness measurement (Fibro-scan score)	At baseline and after 12 weeks of intervention
Liver Panel	Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) will be evaluated in U/L	after 12 weeks of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR	Homeostatic Model Assessment of Insulin Resistance	after 12 weeks of intervention
8-OHdG	Serum level of 8-OHdG	after 12 weeks of intervention
TNF-Alpha	Serum level of TNF-Alpha	after 12 weeks of intervention
hyaluronic acid	Serum level of hyaluronic acid	after 12 weeks of intervention
TGF-β1	Serum level of TGF-β1	after 12 weeks of intervention
Assessment of drugs tolerability: Side effects	Side effects of montelukast	after 12 weeks of intervention

Collaborators and Investigators

• Sponsor: Sadat City University

Publications and helpful links

General Publications

• Abdallah MS, Eldeen AH, Tantawy SS, Mostafa TM. The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. Eur J Pharmacol. 2021 Sep 5;906:174295. doi: 10.1016/j.ejphar.2021.174295. Epub 2021 Jun 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: August 31, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 002017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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