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

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ClinicalTrials.gov Identifier: NCT02484248
Recruitment Status : Recruiting
First Posted : June 29, 2015
Last Update Posted : August 6, 2018
Sponsor:
Information provided by (Responsible Party):
Craig A. Friesen, MD, Children's Mercy Hospital Kansas City

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.

Condition or disease Intervention/treatment Phase
Functional Dyspepsia Drug: Ketotifen Drug: Placebo Phase 3

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  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind, Placebo-controlled, Cross-over Trial of Ketotifen in Children and Adolescents With Functional Dyspepsia in Association With Duodenal Eosinophilia
Actual Study Start Date : August 2015
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02484248


Contacts
Contact: Craig A Friesen, M.D. 816-302-3057 cfriesen@cmh.edu
Contact: Amber Bagherian, MS 816-802-1176 abagherian@cmh.edu

Locations
United States, Missouri
The Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Amber Bagherian, MS    816-802-1176    abagherian@cmh.edu   
Principal Investigator: Craig A Friesen, MD         
Sub-Investigator: Jennifer Colombo, MD         
Sub-Investigator: Jennifer V Schurman, PhD         
Sub-Investigator: Amanda D Deacy, PhD         
Sub-Investigator: Susan Abdel-Rahman, PharmD         
Sponsors and Collaborators
Children's Mercy Hospital Kansas City

Publications:

Responsible Party: Craig A. Friesen, MD, Division Chief Gastroenterologist, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT02484248     History of Changes
Other Study ID Numbers: 14110467
First Posted: June 29, 2015    Key Record Dates
Last Update Posted: August 6, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Craig A. Friesen, MD, Children's Mercy Hospital Kansas City:
pediatric
eosinophilia
duodenal
ketotifen
functional dyspepsia

Additional relevant MeSH terms:
Dyspepsia
Gastritis
Eosinophilia
Signs and Symptoms, Digestive
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Leukocyte Disorders
Hematologic Diseases
Ketotifen
Antipruritics
Dermatologic Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Allergic Agents