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

NCT02360696 | Completed

• 1 other identifier: 13100348
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

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:

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

Conditions

Eosinophilia; Dyspepsia

Keywords

Duodenal Eosinophilia; Functional Dyspepsia; Mucosal Eosinophilia

Outcome Measures

Primary Outcomes (1)

• Identification of a signature of montelukast response using gene expression patterns in biopsy samples from clinical responders and non-responders to montelukast.

  Identification of patients who will benefit from montelukast therapy , allowing more efficient, and possibly more effective, care.

  Approximately 7-8 weeks

Secondary Outcomes (1)

• 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.

Study Arms (1)

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.

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead

Study Sites (1)

Children's Mercy

Kansas City, Missouri, 64108, United States

Location

Related Publications (41)

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Biospecimen

Retention: SAMPLES WITH DNA

Samples retained, with potential for extraction of DNA from at least one of the types of samples retained.

MeSH Terms

Conditions

Eosinophilia; Dyspepsia

Condition Hierarchy (Ancestors)

Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Chief/Division of Gastroenteroly, Hepatology, and Nutrition

Study Record Dates

• First Submitted: September 3, 2014
• First Posted: February 11, 2015
• Study Start: August 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

US (1)