Ketotifen for Children With Functional Dyspepsia in Association With Duodenal Eosinophilia

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.

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.