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WithdrawnNCT03280342Updated Nov 1, 2019

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

A Phase 2 interventional study of IR-TPM (Topamax) and XR-TPM (Trokendi XR) in Migraine and Headache, sponsored by University of Minnesota. Withdrawn at 2 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-11-01.

Sponsored by University of Minnesota · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Sponsor terminated study
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Migraine
  • Headache

Keywords

  • Migraine
  • Headache
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Participant)
Enrollment
0 participants (actual)

Study arms

  • Active comparator
    IR-TPM (Topamax)

    IR-TPM (Topamax)

    Drug: IR-TPM (Topamax) · Drug: XR-TPM (Trokendi XR)

  • Active comparator
    XR-TPM (Trokendi XR)

    Drug: IR-TPM (Topamax) · Drug: XR-TPM (Trokendi XR)

Interventions

  • DrugIR-TPM (Topamax)

    XR-TPM (Trokendi XR)

  • DrugXR-TPM (Trokendi XR)

    XR-TPM (Trokendi XR)

05

What researchers measure

Primary outcomes

  1. Controlled Oral Word Association Test (COWA)-generative phonemic fluency

    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

    Time frame: Baseline (Day 1) through Day 52

Secondary outcomes

  1. Measures of semantic verbal fluency

    Change in scores from individual baseline to each post-dose assessment on measures of semantic verbal fluency (e.g., Animals)

    Time frame: Baseline (Day 1) through Day 52

  2. Digit Span Backward

    Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)

    Time frame: Baseline (Day 1) through Day 52

  3. Digit Symbol Modalities Test (SDMT)

    Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed

    Time frame: Baseline (Day 1) through Day 52

  4. Trails A & B

    Change in scores from individual baseline to each post-dose assessment on measures of executive function

    Time frame: Baseline (Day 1) through Day 52

06

Study locations

2 sites
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Prism Research
    Saint Paul, Minnesota 55114, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03280342
Lead sponsor
University of Minnesota
Collaborators
Supernus Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Sep 12, 2017
Start date
Oct 30, 2017
Primary completion
Aug 20, 2018
Completion
Sep 13, 2018
Last update
Nov 1, 2019

Study contacts

Susan Marino, PhD
principal investigator · University of Minnesota

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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