Investigation the Safety and Efficacy of The Antileukotriene Agents, Montelukast, as Adjuvant Therapy in Obese Patients With Type 2 Diabetes Mellitus

Investigation the Safety and Efficacy of The Antileukotriene Agents, Montelukast, as Adjuvant Therapy in Obese Patients With Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

The aim of the current study is to evaluate the safety and efficacy of Montelukast in treatment of obese patients with type 2 diabetes (T2DM).

Study Overview

• Status: Completed
• Conditions: Obesity; Endocrine; Diabetes Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Montelukast 10mg

Detailed Description

Growing evidences have pointed to the role of 5-lipooxygenase / leukotriene pathway in the pathogenesis of diabesity. Cysteinyl leukotrienes (Cys-LT) are potent inflammatory lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. They act on Cys-LT receptors that are primarily present in the spleen, blood leukocytes, and lung macrophages and are involved in mediation of inflammation. 5-lipoxygenase products exert potent proinflammatory actions, such as induction of nuclear factor (NF) - kB and secretion of proinflammatory and insulin resistant adipokines (i.e., monocyte chemotactic protein-1, tumor necrosis factor-a, macrophage inflammatory protein-1, and interleukin-6) that could potentially contribute to systemic insulin resistance. Furthermore, the physiological consequences of these changes in adipose tissue function were corroborated in vivo by the observation that inhibition of the 5-lipoxygenase pathway reduced proinflammatory cytokines and circulating free fatty acid concentrations, as well as alleviated insulin resistance and hepatic steatosis in experimental obesity.

Montelukast is a Cys-LT1-receptor antagonist that blocks the proinflammatory action of LTD4 . Montelukast is approved for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It acts by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Shebin Elkom, Egypt
    • Faculty of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- type 2 diabetic patients who had body mass index (BMI) ≥ 30 kg/m2 , were treated with metformin alone and had ages ranging from 18 to 60 years.

Exclusion Criteria:

• patients who had any other inflammatory disease
• patients with cardiovascular,
• patients with asthma
• patients with severe hepatic
• patients with renal disease,
• patients with epilepsy
• pregnant or lactating females.

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; 50 patients will receive metformin up to 2000mg/daily (Control group)	Drug: Placebo; Placebo tablet once daily
Experimental: Montelukast group; 50 patients will receive a combination of metformin up to 2000 mg/daily and montelukast (10 mg /day).	Drug: Montelukast 10mg; Montelukast is an orally dosed drug (available as a chewable tablet) which is FDA-approved for the treatment of chronic asthma and prophylaxis and the prevention of exercise-induced bronchoconstriction. It is also approved for the relief of symptoms of both seasonal and perennial allergic rhinitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	HbA1c	From baseline to 12 weeks
Percent change in body weight	Body Weight	From baseline to 12 weeks
BMI	body mass index	From baseline to 12 weeks
Visceral Adiposity Index	visceral fat	From baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adiponectin	Serum level of adiponectin	At baseline to 12 weeks
TNF-α	Serum level of Tumor necrosis factor alpha (TNF-α)	At baseline to 12 weeks
IL-6	Serum level of interleukin-6 (IL-6)	At baseline to 12 weeks
leukotriene B4	Serum level of leukotriene B4 (LTB4)	At baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Sadat City University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): April 10, 2023

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; 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: 7-2021INTM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes