Ketotifen for Children With Functional Dyspepsia in Association With Duodenal Eosinophilia

NCT02484248 | Recruiting Phase 3 FDA Drug

• 1 other identifier: 14110467
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Functional Dyspepsia

Keywords

pediatric; eosinophilia; duodenal; ketotifen; functional dyspepsia

Outcome Measures

Primary Outcomes (7)

• Complete Physical

  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

  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)

  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

  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

  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

  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

  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 Outcomes (2)

• Pharmacokinetic Sampling (Area under the plasma concentration versus time curve - AUC)

  day 0, day 28, day 63, and day 147

• Pharmacokinetics Sampling (Peak Plasma Concentration - Cmax)

  day 0, day 28, day 63, and day 147

Study Arms (2)

cross-over of Ketotifen

ACTIVE COMPARATOR

Patients will begin the active ketotifen treatment first and cross over to placebo.

Drug: Ketotifen

cross-over of Placebo

PLACEBO COMPARATOR

Patients will begin the placebo treatment first and cross over to the active ketotifen.

Drug: Placebo

Interventions

Ketotifen DRUG

Ketotifen is an anti-histamine approved by the U.S. FDA to prevent and treat itching of the eyes caused by allergies.

cross-over of Ketotifen

Placebo DRUG

The placebo tablet looks identical to the ketotifen tablet, but does not contain ketotifen.

cross-over of Placebo

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Craig A. Friesen, MD: lead

Study Sites (1)

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

RECRUITING

Related Publications (11)

• McFadyen ML, Miller R, Ludden TM. Ketotifen pharmacokinetics in children with atopic perennial asthma. Eur J Clin Pharmacol. 1997;52(5):383-6. doi: 10.1007/s002280050305.

  PMID: 9272408 BACKGROUND

• Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010 Sep;59(9):1213-21. doi: 10.1136/gut.2010.213108. Epub 2010 Jul 21.

  PMID: 20650926 BACKGROUND

• Schurman JV, Singh M, Singh V, Neilan N, Friesen CA. Symptoms and subtypes in pediatric functional dyspepsia: relation to mucosal inflammation and psychological functioning. J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):298-303. doi: 10.1097/MPG.0b013e3181d1363c.

  PMID: 20479684 BACKGROUND

• Hall W, Buckley M, Crotty P, O'Morain CA. Gastric mucosal mast cells are increased in Helicobacter pylori-negative functional dyspepsia. Clin Gastroenterol Hepatol. 2003 Sep;1(5):363-9. doi: 10.1053/s1542-3565(03)00184-8.

  PMID: 15017654 BACKGROUND

• Friesen CA, Lin Z, Singh M, Singh V, Schurman JV, Burchell N, Cocjin JT, McCallum RW. Antral inflammatory cells, gastric emptying, and electrogastrography in pediatric functional dyspepsia. Dig Dis Sci. 2008 Oct;53(10):2634-40. doi: 10.1007/s10620-008-0207-0. Epub 2008 Mar 5.

  PMID: 18320315 BACKGROUND

• Friesen CA, Neilan NA, Schurman JV, Taylor DL, Kearns GL, Abdel-Rahman SM. Montelukast in the treatment of duodenal eosinophilia in children with dyspepsia: effect on eosinophil density and activation in relation to pharmacokinetics. BMC Gastroenterol. 2009 May 11;9:32. doi: 10.1186/1471-230X-9-32.

  PMID: 19432972 BACKGROUND

• Santos J, Saperas E, Nogueiras C, Mourelle M, Antolin M, Cadahia A, Malagelada JR. Release of mast cell mediators into the jejunum by cold pain stress in humans. Gastroenterology. 1998 Apr;114(4):640-8. doi: 10.1016/s0016-5085(98)70577-3.

  PMID: 9516384 BACKGROUND

• Stefanini GF, Saggioro A, Alvisi V, Angelini G, Capurso L, di Lorenzo G, Dobrilla G, Dodero M, Galimberti M, Gasbarrini G, et al. Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients. Scand J Gastroenterol. 1995 Jun;30(6):535-41. doi: 10.3109/00365529509089786.

  PMID: 7569760 BACKGROUND

• Chen X, Zhong D, Liu D, Wang Y, Han Y, Gu J. Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study. Rapid Commun Mass Spectrom. 2003;17(22):2459-63. doi: 10.1002/rcm.1189.

  PMID: 14608613 BACKGROUND

• Grahnen A, Lonnebo A, Beck O, Eckernas SA, Dahlstrom B, Lindstrom B. Pharmacokinetics of ketotifen after oral administration to healthy male subjects. Biopharm Drug Dispos. 1992 May;13(4):255-62. doi: 10.1002/bdd.2510130404.

  PMID: 1600111 BACKGROUND

• Friesen CS, Shakhnovich V, Toren P, Retke B, Schurman J, Colombo J, Deacy A, Friesen CA, Abdel-Rahman S. A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia. Paediatr Drugs. 2024 Jul;26(4):451-457. doi: 10.1007/s40272-024-00628-8. Epub 2024 May 21.

  PMID: 38771467 DERIVED

MeSH Terms

Conditions

Eosinophilia

Interventions

Ketotifen

Condition Hierarchy (Ancestors)

Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Craig A Friesen, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Craig A Friesen, M.D.

CONTACT

816-234-3066; cfriesen@cmh.edu

Amber Bagherian, MS

CONTACT

816-234-3066; abagherian@cmh.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Division Chief Gastroenterologist

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: June 29, 2015
• Study Start: August 1, 2015
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)