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

Sponsor

Children's Mercy Hospital Kansas City (Other)

Overall Status

Completed

CT.gov ID

NCT02360696

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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:

systemic drug exposure (drug absorption, biotransformation and/or elimination)
regulation of leukotriene biosynthesis
cysteinyl leukotriene receptors and downstream mediators
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.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilia Dyspepsia

Study Design

Study Type:

Observational

Actual Enrollment :

18 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Predictors of Clinical Response to Montelukast in Children With Functional Dyspepsia

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Mercy	Kansas City	Missouri	United States	64108

Sponsors and Collaborators

Children's Mercy Hospital Kansas City

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