Clinical trial NCT03280342: Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine
Official title: Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Migraine
Headache
Keywords: Migraine
Headache
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Supernus Pharmaceuticals, Inc.
First posted: 2017-09-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: a crossover, randomized, double blind design in conjunction with intensive pharmacokinetic sampling and multiple administrations of a neurocognitive test battery to directly compare the effects on cognition of IR-TPM to XR-TPM in adults with migraine. The dose will begin at 25mg and titrated in 25mg increments to reach target dose of 100mg.
Primary purpose: TREATMENT

Brief summary: Crossover, randomized, double blind: Q12h dosing in both periods; matching placebo for evening dosing during XR treatment; target dose: 100mg

Detailed description: The primary objective is to compare the effect of treatment with an immediate-release topiramate (IR-TPM), namely Topamax®, to an extended-release topiramate (XR-TPM), namely Trokendi XR®, regimen on cognition in adults with migraine.

The secondary objective is to determine the factors that explain inter-individual variability in cognitive response. Pharmacokinetic and demographic factors will be explored. Variability in cognitive response between individuals can be large. A population approach (nonlinear, mixed effects) will be used to determine drug exposure response relationships.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Male or female, ages 18-65
3. 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.
4. 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.
5. Native English speakers (due to speech and language analysis)
6. Montreal Cognitive Assessment (MoCA) score equal to or greater than 26.

Exclusion Criteria:

1. 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.
2. 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.
3. A history of nephrolithiasis
4. Have previously taken topiramate
5. Received an experimental drug or used an experimental or approved device for migraine prevention (e.g., TENIS unit) within 30 days of screening

Primary outcomes:
measure: Controlled Oral Word Association Test (COWA)-generative phonemic fluency
timeFrame: Baseline (Day 1) through Day 52
Secondary outcomes:
measure: Measures of semantic verbal fluency
timeFrame: Baseline (Day 1) through Day 52
measure: Digit Span Backward
timeFrame: Baseline (Day 1) through Day 52
measure: Digit Symbol Modalities Test (SDMT)
timeFrame: Baseline (Day 1) through Day 52
measure: Trails A & B
timeFrame: Baseline (Day 1) through Day 52
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Susan Marino, PhD
role: PRINCIPAL_INVESTIGATOR
References: