Montelukast decrease dyspeptic symptoms in patients with Functional Dyspepsia

Registration number: NPCTR2021000014
Register By : Dr Mohan Bhusal
Registered Date : 2021/04/18
Email : mohan.drbhusal7@gmail.com
Titles & IDs
Refrence Number : REF/2021/04/000068
Public Title : Montelukast decrease dyspeptic symptoms in patients with Functional Dyspepsia
Scientific Title : Effectiveness of Montelucast in Functional Dyspeptic patients with Duodenal Eosinophilia: A Randomized Controlled trial
Trial Acronyms :
Registration Type : Prospective
Secondary Id :
Recruitment Country : Nepal

Dyspepsia refers to a group of symptoms that originate from the gastroduodenal region. Dyspeptic symptoms are epigastric pain, epigastric burning, postprandial fullness, early satiation, and others, including bloating in the upper abdomen, nausea, vomiting, and belching. Functional Dyspepsia (FD), a relapsing and remitting disorder, is one of the most commonly diagnosed Functional Gastrointestinal Disorder’s (FGIDS). Global prevalence of uninvestigated dyspepsia is varies from 21-30%, although it varies with geographical location, diagnostic criteria, and symptom duration.

FD is a commonest cause of dyspepsia in Asian population. FD as defined by ROME IV is a chronic or intermittent disorder characterized by one or more of the four main symptoms: postprandial fullness, early satiety, epigastric pain and/or epigastric burning, without organic or metabolic explanation after routine clinical examination and upper GI Endoscopy.FD is often misdiagnosed or over diagnosed. It requires differentiation from other conditions primarily presenting as dyspepsia.

There is no short cut, algorithm or simple guidelines except recording a good history and a detail examination by a Gastro-physician having expertise and interest in dyspepsia. Despite extensive investigation, the underlying causes of dyspepsia in a majority of patients remain unknown. Friesen CA et al., reported a positive clinical response of 62.1% in patients receiving Montelucast compared with 32.4% on placebo. In study by Pamela DB et al. reported a successful relief of dyspeptic symptoms with omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) in a patients with FD.

Montelukast is a selective antagonist of the leukotriene receptor. It is found that LTC4, LTD4 and LTE4 all binds with CysLT1 receptors which can be competitively antagonized by Montelukast. Montelukast, a competitive antagonist of cys LT1 receptor, used for the treatment of eosinophilic gastroenteritis, is found to relieve dyspeptic symptoms in children with duodenal eosinophilia.

U.S. Food and Drug Administration have approved use of Montelukast use in pediatrics and Adult.Cysteinyl-leukotrienes (cys-LTs) also alter mast cell function. Cys-LTs induce IL-5 and TNF-α production in primed mast cells, an effect blocked by cys-LT inhibition. Montelukast's effect may also involve other inflammatory cells as montelukast has been shown to down regulate human monocyte chemotaxis induced by MCP-1.

Leukotrienes also have the potential to alter gastrointestinal tract function and produce symptoms such as pain by mechanisms which might include alteration/modulation of sensory and motor neuron function and possibly, increasing susceptibility to insult via cellular injury or changes in local blood flow.

LTD4 receptors after activation produce smooth muscle contraction, increased vascular permeability, increased mucus secretion.It is also a potent and selective chemoattractant for human eosinophils. Drugs that interfere with eosinophilic chemotactic signals might prove useful. For example, leukotriene-receptor antagonists, such as Montelukast, prevent the binding of potent leukotrienes that act as eosinophil chemoattractants. The use of a humanized monoclonal antibody against interleukin-5 (an eosinophil and inflammatory mediator) in hypereosinophil syndromes appears to have been effective in an initial small clinical trial.

The primary objective of these study is to determine the effectiveness of Montelucast to reduce dyspeptic symptoms in functional dyspeptic patients with duodenal eosinophilia. The other objective is to determine the effect of Montelukast and Proton pump inhibitors on duodenal Eosinophil density in same patients. Similarly, others objectives are to evaluate the adverse effects of Montelukast and to review the demographical and clinical spectrum of the patients with FD.

Principal Investigator (Trail coordinator for multi centric study)

Principal Investigator ( 1 )

Name
Dr. Mohan Bhusal
Email
mohanbmaxx7@gmail.com
Contact No
9857036456
Designation
DM-Resident of Gastroenterology
Orgnizational Affilation
TUTH-IOM
Address
Maharajgunj, Kathmandu
Country
Nepal

Contact person (scientific query)
Name
Dr. Mohan Bhusal
Email
mohanbmaxx7@gmail.com
Contact No
9857036456
Designation
DM-Resident of Gastroenterology
Orgnizational Affilation
TUTH-IOM
Address
Maharajgunj, Kathmandu
Country
Nepal

Contact person (Public Query)
Name
Dr. Mohan Bhusal
Email
mohanbmaxx7@gmail.com
Contact No
9857036456
Designation
DM-Resident of Gastroenterology
Orgnizational Affilation
TUTH-IOM
Address
Maharajgunj, Kathmandu
Country
Nepal

Contact person (Public Query)
Name
Dr. Mohan Bhusal
Email
mohanbmaxx7@gmail.com
Contact No
9857036456
Designation
DM-Resident of Gastroenterology
Orgnizational Affilation
TUTH-IOM
Address
Maharajgunj, Kathmandu
Country
Nepal

Sponsor
Type
Pharmaceutical industry
Name
Quest pharmaceutical
Email
quest.ktm@quest.com.np
Contact
9855065439
Address
Daan sadan, Teku, Kathmandu

Recruitment Country
Country
Nepal

Site(s) of study
Site Address
IOM-Maharajgunj
Contact Person Name
Dr Mohan Bhusal
Contact Person Email
mohanbmaxx7@gmail.com
Contact Person Contact
9857036456

Ethics Committees Informations
Ethics Committee
Ethics Committee Contact
Ethics Committee Address
Ethics Committee Email

Approvals
Status
Submitted/ Under review
Date
2021-01-13

Health condition(s)
Status
Particular health condition(s) or problem(s)

Study type
Thesis
Yes
Type of trial
Interventional
Study Type
Preventive, Preventive, Drug,

Study Design
Allocation
randomized controlled trial
Masking
blinded (masking used)
Control
active
Assignment
parallel
purpose
treatment
Trial Phase
4

Intervention and comparison
Intervention name
Montelukast Vs PPI Functional dyspepsia
Intervention details
  • All patients included in these study will undergo an initial endoscopy as part of a routine clinical evaluation. Standard biopsies will be obtained from Antrum and duodenum from all patients. Helicobacter pyloric infection will be excluded by histology. Biopsy obtained from Duodenum will be sent for Eosinophil count. In a patient’s with eosinophil count ≥ 22/5HPF, Montelucast (10mg once a day for one group) and usual standard care of treatment (PPI for another group) will be given for a period of month. Treatment group and control groups will be assigned through computer generated random number. Each participant will be given a concealed envelope with assignment of treatment or control group. Data collection will be conducted until the desired sample is met.
Comparison name
Montelukast Vs PPI Functional dyspepsia
Comparison details
  • Patients diagnosed as Functional Dyspepsia using ROME IV will be included. Each patient diagnosed as Functional Dyspepsia will be subjected to a detail clinical history regarding duration of illness and symptoms. Predetermined proforma will be used as the tool for data collection. Data will be collected from all patients who provide written informed consent.
  • Each patient will be subjected to a detail systemic examination. All patients will undergo an initial endoscopy as part of a routine clinical evaluation. Standard biopsies will be obtained from Antrum and duodenum from all patients. Helicobacter pyloric infection will be excluded by histology. Biopsy obtained from Duodenum will be sent for Eosinophil count. In a patient’s with eosinophil count ≥ 22/5HPF, Montelucast (10mg once a day for one group) and usual standard care of treatment (PPI for another group) will be given for a period of month. Treatment group and control groups will be assigned through computer generated random number. Each participant will be given a concealed envelope with assignment of treatment or control group. Data collection will be conducted until the desired sample is met. After one month response will be assessed by clinical and histological response. Compliance will be assessed by examination of the daily diary kept by each subject/parent and tablet counts at the end of each treatment period.

Eligibility (Inclusion criteria)
Age Group
Age > 18 years
Gender
Both
Detail
  • All cases of Functional Dyspeptic patients according to Rome IV criteria
  • Eosinophilia on Duodenal Biopsy
  • Those who provide consent
Exclusion Detail
  • Patients with organic dyspepsia
  • Pregnant woman
  • Age < 18 years
  • Use of leukotriene receptor antagonists (LTRA) or corticosteroids in the last month
  • Use of PPI in last two weeks.
  • H pylori positive
Sample Size
43 case and control each
Enrollment Date
2021-05-01
Completion Date
2022-05-31
Enrollment Status
Pending