Ketotifen for Children With Functional Dyspepsia in Association With Duodenal Eosinophilia (Ketotifen)

September 19, 2023 updated by: Craig A. Friesen, MD, Children's Mercy Hospital Kansas City

Double-blind, Placebo-controlled, Cross-over Trial of Ketotifen in Children and Adolescents With Functional Dyspepsia in Association With Duodenal Eosinophilia

Acid reduction remains the most common treatment prescribed empirically by pediatric gastroenterologists for children with functional dyspepsia (FD). When acid reduction therapy fails to provide patients with a therapeutic effect, ketotifen and cromolyn, mast cell stabilizers, represent an attractive potential therapy given data implicating mast cells in the generation of dyspeptic symptoms. Although there have been no adult or pediatric studies on the use of mast cell stabilizers in patients with FD, benefit has been demonstrated in adults with IBS and children with eosinophilic gastroenteritis. Additionally, previous studies show mucosal eosinophilia is highly correlated with functional dyspepsia. Our usual current treatment pathway for functional dyspepsia in association with duodenal mucosal eosinophilia is as follows: acid-reducing medication/montelukast → addition of H1 antagonist → addition of budesonide → addition of oral cromolyn. If ketotifen is effective, it offers the advantage of being able to replace both the H1 antagonist and the oral cromolyn at a substantially reduced cost (approximately 10% of the cost of cromolyn alone). This study aims to introduce ketotifen earlier in the treatment pathway to examine its efficacy on children with functional dyspepsia in association with duodenal eosinophilia.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a double-blind, placebo-controlled, cross-over trial of ketotifen in children ages 8 through 17 inclusive that have a diagnosis of functional dyspepsia and have had continued abdominal pain despite acid reduction therapy in combination with montelukast. The primary aim is to assess the symptomatic response to ketotifen as compared to placebo in children with functional dyspepsia in association with duodenal eosinophilia who have previously had worsening, no clinical change, or only a partial response to acid-reduction therapy in combination with montelukast.

The study lasts 147 days for subjects responsive to ketotifen and 63 days for those who are not. For those who respond to ketotifen, there are 4 clinic visits and 3 phone interviews. Clinic visits include a physical, blood draws, questionnaires, review of medical history and medications; phone interviews involve answering a few questions. For those who do not respond to ketotifen, there are 3 clinic and 2 phone visits. Subjects who enroll in the study are randomly assigned to Group A or Group B. The subject, subject's parents, and study staff will not know to which group the subject is assigned. Group A will be given a placebo, an inactive pill with no medication in it, for days 1-28, and switched to ketotifen for days 36-63. Group B will be given ketotifen for days 1-28 and switched to placebo for days 36-63. The group assignment will be unblinded at day 63, at which point initial ketotifen responders will undergo an open-label twelve week trial of ketotifen to assess sustainability.

Secondary aims of this study include assessing the impact of ketotifen on quality of life, state and trait anxiety, and whether baseline trait anxiety is predictive of clinical response to ketotifen. The study will also assess whether functional dyspepsia subtype is predictive of response to ketotifen, the sustainability of response to ketotifen in initial responders, and the pharmacokinetics of ketotifen in this patient population.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

  • Name: Craig A Friesen, M.D.
  • Phone Number: 816-234-3066
  • Email: cfriesen@cmh.edu

Study Contact Backup

Study Locations

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

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

6 years to 15 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. between the ages of 8 and 17 years, inclusive
  2. abdominal pain of at least 8 weeks duration and fulfilling symptom-based criteria for functional dyspepsia(5);
  3. previous endoscopy with biopsies demonstrating >20 eosinophils/high powered field on duodenal mucosal biopsies;
  4. previous treatment with acid-reduction therapy and montelukast with a level 3 (as defined below)or lesser response;
  5. evidence of written parental permission (consent) and subject assent;
  6. Negative pregnancy screening for females of child bearing potential.

Exclusion Criteria:

  1. previous treatment with ketotifen;
  2. treatment with corticosteroids or oral cromolyn sodium in the four weeks prior to enrollment;
  3. any prior history of diabetes mellitus, cancer, chronic cardiac disease, respiratory disease, or renal disease requiring routine medical care;
  4. Pregnant/planning to become pregnant;
  5. Post-menarche females unwilling to use highly-efficacious contraception to prevent pregnancy;
  6. Epilepsy or history of seizures;
  7. Liver disease or elevation of liver enzymes;
  8. Use of oral hypoglycemic medications, antipsychotics, benzodiazepines, tricyclic antidepressants, barbiturates, or opioids;
  9. Allergy to ketotifen or other products in capsule
  10. Refusal of Urine pregnancy test in post-menarchal females.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: cross-over of Ketotifen
Patients will begin the active ketotifen treatment first and cross over to placebo.
Drug: Ketotifen
Ketotifen is an anti-histamine approved by the U.S. FDA to prevent and treat itching of the eyes caused by allergies.
Placebo Comparator: cross-over of Placebo
Patients will begin the placebo treatment first and cross over to the active ketotifen.
Drug: Placebo
The placebo tablet looks identical to the ketotifen tablet, but does not contain ketotifen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Physical
Time Frame: day 0, day 28, day 63, and day 147
The study physician will check all systems and ask questions about pain and symptoms. This is a comprehensive system check to ensure safety. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
Blood pressure
Time Frame: day 0, day 28, day 63, and day 147
A trained professional will measure blood pressure to ensure value is within normal range and ensure safety of patient. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
Liver Functioning Test (a test ran from a blood sample to check a patients liver functioning)
Time Frame: day 0, day 28, day 63, and day 147
A blood sample is collected and tested by a certified laboratory for liver function. This will be completed and verified to be within normal ranges by the study physician to ensure patient safety. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
State-Trait Inventory for Cognitive and Somatic Anxiety - Child Version
Time Frame: day 0, day 28, day 63, and day 147
Anxiety score testing assessed with questionnaires. Anxiety scores are correlated with pain. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
Pediatric Quality of Life Inventory
Time Frame: day 0, day 28, day 63, and day 147
Quality of life survey for pediatrics to ensures maintenance of quality of life throughout study. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
Heart Rate
Time Frame: day 0, day 28, day 63, and day 147
A trained professional will measure heart rate to ensure value is within normal range and patient safety. Change is assessed from each time period.
day 0, day 28, day 63, and day 147
Respiratory Rate
Time Frame: day 0, day 28, day 63, and day 147
A trained professional will measure respiratory rate to ensure value is within normal range and patient safety. Change is assessed from each time period.
day 0, day 28, day 63, and day 147

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic Sampling (Area under the plasma concentration versus time curve - AUC)
Time Frame: day 0, day 28, day 63, and day 147
Pharmacokinetic sampling allows for evaluation of the entire process of the drug breakdown by the body and ensures long term efficacy and safety. Change is being assessed from each time period.
day 0, day 28, day 63, and day 147
Pharmacokinetics Sampling (Peak Plasma Concentration - Cmax)
Time Frame: day 0, day 28, day 63, and day 147
Pharmacokinetic sampling allows for evaluation of the entire process of the drug breakdown by the body and ensures long term efficacy and safety. Change is being assessed from each time period.
day 0, day 28, day 63, and day 147

Collaborators and Investigators

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

Sponsor

Children's Mercy Hospital Kansas City

Investigators

  • Principal Investigator: Craig A Friesen, MD, Children's Mercy Hospital Kansas City

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 (Actual)

August 1, 2015

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

January 13, 2015

First Submitted That Met QC Criteria

June 24, 2015

First Posted (Estimated)

June 29, 2015

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 19, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14110467

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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