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

Primary Purpose

Migraine, Headache

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IR-TPM (Topamax)
XR-TPM (Trokendi XR)
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Migraine focused on measuring Migraine, Headache

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Minnesota
  • Prism Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

IR-TPM (Topamax)

XR-TPM (Trokendi XR)

Arm Description

IR-TPM (Topamax)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)
Digit Span Backward
Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)
Digit Symbol Modalities Test (SDMT)
Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed
Trails A & B
Change in scores from individual baseline to each post-dose assessment on measures of executive function

Full Information

First Posted
September 1, 2017
Last Updated
October 30, 2019
Sponsor
University of Minnesota
Collaborators
Supernus Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03280342
Brief Title
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

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor terminated study
Study Start Date
October 30, 2017 (Actual)
Primary Completion Date
August 20, 2018 (Actual)
Study Completion Date
September 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
Supernus Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine, Headache
Keywords
Migraine, Headache

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IR-TPM (Topamax)
Arm Type
Active Comparator
Arm Description
IR-TPM (Topamax)
Arm Title
XR-TPM (Trokendi XR)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
IR-TPM (Topamax)
Intervention Description
XR-TPM (Trokendi XR)
Intervention Type
Drug
Intervention Name(s)
XR-TPM (Trokendi XR)
Intervention Description
XR-TPM (Trokendi XR)
Primary Outcome Measure Information:
Title
Controlled Oral Word Association Test (COWA)-generative phonemic fluency
Description
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 Outcome Measure Information:
Title
Measures of semantic verbal fluency
Description
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
Title
Digit Span Backward
Description
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
Title
Digit Symbol Modalities Test (SDMT)
Description
Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed
Time Frame
Baseline (Day 1) through Day 52
Title
Trails A & B
Description
Change in scores from individual baseline to each post-dose assessment on measures of executive function
Time Frame
Baseline (Day 1) through Day 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Marino, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Prism Research
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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