Functional Dyspepsia (FD) - Clinical Response to Montelukast in Children

May 15, 2019 updated by: Craig A. Friesen, MD, Children's Mercy Hospital Kansas City

Predictors of Clinical Response to Montelukast in Children With Functional Dyspepsia

Duodenal eosinophilia has been associated with dyspepsia in adults and the investigators have previously described the finding of duodenal mucosal eosinophilia in 71-79% of children undergoing diagnostic endoscopy. Previous studies in children have shown positive response to montelukast with approximately 50% finding complete relief and 20-30 percent showing no response.

There are a number of factors that have the potential to contribute to the observed variability in response to montelukast. These include variability in:

  1. systemic drug exposure (drug absorption, biotransformation and/or elimination)
  2. regulation of leukotriene biosynthesis
  3. cysteinyl leukotriene receptors and downstream mediators
  4. patient disease phenotype (e.g. Functional Gastrointestinal Disorder (FGID) disease classification, psychologic profile)

In this study, the investigators propose to utilize biopsy specimens stratified by drug response to identify candidate gene expression modules that will be validated in a prospective study design. The overall goal of this program is to develop a signature of montelukast response that can be applied not only to eosinophilic gastroenteritis, but more generally to other diseases, such as asthma, where the drug is widely used with variable success.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

18

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Up to 50 subjects (allowance of 20 additional subjects for screen fails and those who will not complete Phase 3 of the study) will be recruited from a cohort of patients referred to the Abdominal Pain Clinic at Children's Mercy Hospitals and Clinics and enrolled prior to routine initial endoscopy.

Description

Inclusion Criteria:

  • Ages 8 - 17 years, inclusive
  • Abdominal pain of at least 8 weeks duration and fulfilling symptom- based criteria for functional dyspepsia
  • Scheduled for endoscopy following failure to respond to acid-reduction therapy
  • Evidence of written parental permission (consent) and subject assent

Exclusion Criteria:

  • Previous treatment with montelukast
  • Treatment with corticosteroids or oral cromolyn sodium in the four weeks prior to enrollment
  • Prior history or clinical signs/symptoms of chronic disease requiring regular medical care (e.g., diabetes mellitus, juvenile idiopathic arthritis, cystic fibrosis or cancer)
  • Exposure within the past two weeks to drugs or natural products that induce CYP2C8/9 or CYP3A4, including amprenavir, carbamazepine, lopinavir/ritonavir, nafcillin, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifampin, St. John's Wort, or that inhibit CYP2C8/9 or CYP3A4, such as ciprofloxacin, clarithromycin, erythromycin, fluconazole, fluvoxamine, grapefruit juice, paroxetine, sertraline, sulfamethoxazole, trimethoprim
  • A Body Mass Index of 30 or greater
  • Non-English speaking
  • Those patients who will turn 18 during the duration of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Peds/Adol Pts w/ FD - CMH GI APT clinic

Phase 1. Standard-of-Care Endoscopy to establish baseline data and immunohistochemistry studies. Additional biopsies taken for DNA and microarray analysis. If participant biopsies meet criteria (> or = 20/hpf) and no nodularity or tumors, s/he will be eligible to move to second phase.

Phase 2. Standard of care treatment of 3 mg/kg ranitidine bid and 20 mg. montelukast each AM for three weeks. Based on response to global assessment score, participants will be placed in non-responder or responder group. Participants from the responder group will move to final phase of the study.

Phase 3: Research endoscopy to measure response to montelukast therapy. Biopsies taken for cell density counts and immunohistochemistry studies. Additional biopsies taken for DNA and microarray analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of a signature of montelukast response using gene expression patterns in biopsy samples from clinical responders and non-responders to montelukast.
Time Frame: Approximately 7-8 weeks
Identification of patients who will benefit from montelukast therapy , allowing more efficient, and possibly more effective, care.
Approximately 7-8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization a signature of montelukast response using comparison gene expression patterns in biopsy samples obtained before and after montelukast therapy in children with a positive clinical response to the drug.
Time Frame: 7-8 weeks.
Identification and development of a signature of montelukast response applied to eosinophilic gastroenteritis, and more generally to other diseases, such as asthma, where the drug is widely used with variable success.
7-8 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Craig A. Friesen, MD, Children's Mercy, Division of Gastroenterlogy, Hepatology, and Nutrition
  • Principal Investigator: Steven Leeder, PharmD, PhD, Children's Mercy, Division of Clinical Pharmacology and Medical Toxicology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

September 3, 2014

First Submitted That Met QC Criteria

February 5, 2015

First Posted (Estimate)

February 11, 2015

Study Record Updates

Last Update Posted (Actual)

May 16, 2019

Last Update Submitted That Met QC Criteria

May 15, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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