Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine

Recruitment & Eligibility

Inclusion Criteria

Established history of episodic migraine with or without aura, as assessed by International Headache Society criteria, for at least 6 months before screening and frequency of 3 or more headache attacks per month during the past 3 months
Male or female, ages 18-65
Women are required to be postmenopausal, surgically incapable of bearing children, or practicing a medically acceptable method of birth control (i.e., double barrier method, IUD, Mirena, etc) for at least 1 month before study entry through 30 days following last dose.
If postmenopausal and on hormone replacement therapy (HRT) then must to be on a stable regimen for at least 2 months (continuous stable regimen of cyclic or non-cyclic HRT); negative pregnancy test.
Native English speakers (due to speech and language analysis)
Montreal Cognitive Assessment (MoCA) score equal to or greater than 26.

Exclusion Criteria

Onset of migraine occurred after age 50 years, or overuse of analgesics or migraine specific agents for the acute treatment of migraine episodes; examples of analgesic overuse included the following: more than 8 treatment episodes (episode defined as any calendar day of usage) of ergot containing medications a month; more than 8 treatment episodes of triptans a month; or more than 6 treatment episodes of potent opioids a month.
Required, continued use of the following medications for any medical reason during the study: beta-blockers, benzodiazepines, tricyclic antidepressants, antiepileptics, calcium channel blockers, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) daily, opioids, agents for insomnia (e.g., Ambien, diphenhydramine-containing OTC products); corticosteroids, local anesthetics, botulinum toxin within last three months, or herbal preparations such as feverfew or St John's wort. However, subjects will be permitted to be on a stable regimen of a selective serotonin reuptake inhibitor or SNRI for 3 months or more for depression and/or anxiety.
A history of nephrolithiasis
Have previously taken topiramate
Received an experimental drug or used an experimental or approved device for migraine prevention (e.g., TENIS unit) within 30 days of screening

Study & Design

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Controlled Oral Word Association Test (COWA)-generative phonemic fluency	Baseline (Day 1) through Day 52	The primary outcome measure is the Controlled Oral Word Association (COWA: phonemic generative fluency). COWA was chosen as the primary endpoint since in previous studies of drug-induced cognitive impairment, this measure was sensitive to the effects of topiramate (Meador et al, 2003; Marino et al, 2012; Marino et al, 2015). The primary endpoint is a change in the COWA score from baseline to each post-dose assessment

Secondary Outcome Measures

Name	Time	Method
Digit Span Backward	Baseline (Day 1) through Day 52	Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)
Measures of semantic verbal fluency	Baseline (Day 1) through Day 52	Change in scores from individual baseline to each post-dose assessment on measures of semantic verbal fluency (e.g., Animals)
Digit Symbol Modalities Test (SDMT)	Baseline (Day 1) through Day 52	Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed
Trails A & B	Baseline (Day 1) through Day 52	Change in scores from individual baseline to each post-dose assessment on measures of executive function

Recruitment & Eligibility