Topiramate for the Prophylactic Treatment of Cyclic Vomiting Syndrome in Children
Topiramate for the Prophylactic Treatment of Cyclic Vomiting Syndrome in Children
The purpose of this study is to assess the effectiveness, tolerability and safety of oral
 topiramate for the preventative management of Cyclic Vomiting Syndrome. It is believed that
 topiramate will decrease the frequency, duration and severity of attacks experienced by
 children and adolescents with Cyclic Vomiting Syndrome.
There is very little controlled data on the preventative treatment for Cyclic Vomiting
 Syndrome. The existing evidence consists of small, retrospective clinical series that
 evaluate symptomatic responses to five medications including cyproheptadine, propranolol,
 amitriptyline, phenobarbital and pizotifen (n >10). These published data consist of
 uncontrolled or retrospective reports. In addition, varying inclusion criteria and outcomes
 (i.e. obtained by family recall) were used in these studies limiting the basis upon which to
 compare relative effectiveness.

 During the prospective baseline period, the subject will maintain cyclical vomiting records
 in which all headache occurrences will be recorded and characterized. (Cyclical vomiting
 records will be maintained throughout the study). The purpose of this study is to assess the
 effectiveness, tolerability and safety of oral topiramate for the preventative management of
 Cyclic Vomiting Syndrome using a prospective design, established diagnostic criteria (ICHD
 2004), and defined, objective primary and secondary endpoints.
Inclusion Criteria:

 -  Meet the2004 ICHD Criteria for Cyclical Vomiting.

 -  1 vomiting attack lasting > 24 hours duration for 3 consecutive months

 -  4-12 years of age.

 -  If female, subjects must:

 1. be premenarchal or otherwise incapable of pregnancy, or

 2. have practiced one of the following methods of contraception for at least one
 month prior to study entry: hormonal contraceptives, spermicide and barrier,
 intrauterine device, partner sterility, or

 3. be practicing abstinence and agree to continue abstinence or to use an acceptable
 method of contraception (as listed above) should sexual activity commence.

 -  Able to take oral medication in tablet form or sprinkle form

 -  Subjects or their guardians must be willing and able to: a) read and comprehend
 written instructions, b) complete the assessment forms, c) return for regular visits,
 and d) adhere to medication regimens.

 -  Subjects (or their legally acceptable representative) must have signed an informed
 consent document

 Exclusion Criteria

 -  Have taken topiramate within 14 days prior to the start of the prospective baseline
 period.

 -  Have taken certain medications for cyclical vomiting prophylaxis

 -  Have progressive neurological disorder or a structural disorder of the brain from
 birth, trauma or past infection.

 -  Subjects who have taken any medications for migraine prophylaxis, within 2 weeks of
 the start of the prospective baseline period.

 -  Subjects starting non-pharmacologic prophylactic approaches (e.g., acupuncture,
 biofeedback, chiropractic methods) within 1 month prior to Visit 1.

 -  Require continuing treatment with anticonvulsant therapy for a non-migraine condition.

 -  Significant major psychiatric disorder (e.g., major depression) or subjects receiving
 anti-psychotic medication.

 -  History of attempted suicide or suicidal tendencies.

 -  History of substance abuse.

 -  Pregnant or lactating females.

 -  Have clinically unstable neurological, cardiovascular, gastrointestinal,
 musculoskeletal, pulmonary or other disease.

 -  Have any disease or condition that could compromise the function of those body systems
 that could result in altered absorption, excess accumulation, or impaired metabolism
 or excretion of the test medications (e.g., abnormal renal and/or hepatic function).

 -  Have active liver disease.

 -  Have received an investigational drug or used an investigational device within 30 days
 of study entry.

 -  Employees of the investigator, study center, or sponsor (i.e., principal investigator,
 sub-investigator(s), study coordinators, other study staff, employees, or contractors
 of each), with direct involvement in the proposed study or other studies under the
 direction of that investigator, study center or sponsor, as well as family members of
 the employees or the investigator.