Cognitive DeficitsPhase 4NCT01889602

Characterizing and Predicting Drug Effects on Cognition

A Phase 4 study testing Lorazepam, Topiramate 100mg and Topiramate 150mg in people with Cognitive Deficits, run by University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Cognitive Deficits
What is being tested?: Lorazepam, Topiramate 100mg and Topiramate 150mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 60 participants
Where: 1 siteUnited States
Study dates: Jul 2013to Aug 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy men and women
Ages 18-50
Women are post-menopausal or using approved birth control methods
To control for brain lateralization of language functions, subjects need to have a dominant right hand.

Who cannot join

Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, renal, neurologic, and/or psychiatric disease including suicidality
Vision or hearing impairments
Current or a history of drug or alcohol abuse
living outside of the Twin Cities Metropolitan area.
The use of concomitant medications known to affect Topiramate (TPM), Lorazepam (LZP), or the use of any concomitant medications that may alter cognitive function
Prior adverse reaction or prior hypersensitivity to TPM, LZP or related compounds
A positive pregnancy test (administered to all women before enrollment, and prior to each study session).
Subjects who have received any investigational drug within the previous 30 days

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Minnesota
Minneapolis, Minnesota, 55414

Other trials in United States

About this study

Cognitive impairment is a widely reported side effect of many commonly used drugs. Even a mild, untoward effect on an essential function such a linguistic behavior, a directly observable product of complex cognitive processes, is disruptive to daily life. Nevertheless, the mechanisms underlying a drug's impact on cognition are poorly understood. This lack of understanding impedes the ability to predict both the effects of drugs in development and the degree to which an individual is vulnerable to the cognitive impact of a particular agent. Topiramate (TPM, an antiepileptic drug) is, with increasing frequency, being prescribed for a range of conditions including migraine prophylaxis, obesity and pain. It is a prime example of a drug that causes speech and language problems severe enough in some patients to result in discontinuation of therapy. For reasons not well understood, TPM has a poorer cognitive profile than many of the older antiepileptic drugs. The investigators' rational for this study is that it will offer insight into the mechanisms underlying drug-induced cognitive deficits.

Read the detailed description

The investigators' long-term goal is to enhance clinical strategies and inform drug development in order to maximize the benefits of individual drug therapy while minimizing adverse cognitive/language-related side effects. The investigators' objective in this application is to elucidate the relationship among drug exposure as measured by plasma drug levels, its neurophysiological effects, and consequent effects on the cognitive processes observable in everyday language use. Using topiramate (TPM) as a prototype, the investigators will apply the tools of clinical pharmacology, computational linguistics, neuroscience, and engineering to the design and execution of randomized, double blind, crossover studies using three (3) doses of TPM, one (1) dose of a comparator drug (lorazepam-LZP) and a placebo. In order to isolate the cognitive effects of TPM from those possibly arising from an underlying medical condition, subjects will be healthy adults. The investigators will capitalize on an innovative system for automated language and speech analysis (SALSA) developed in our laboratory, to quantify the effects of TPM administration on effective language use, a crucial component of normal day-to-day functioning.

Conditions: Cognitive Deficits
Being tested: Lorazepam, Placebo, Topiramate 100mg, Topiramate 150mg, Topiramate 200mg
Keywords: Healthy volunteers, Topiramate, Neurocognition, Drug-induced cognitive deficits
Medical subject headings: Cognition Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LorazepamDrug
Also called Ativan
Lorazepam: 2mg, po, 1x
PlaceboOther
Non-active placebo, po, 1x
Topiramate 100mgDrug
Also called Topamax
Topiramate: 100 mg, po, 1x
Topiramate 150mgDrug
Also called Topamax
Topiramate: 150 mg, po, 1x
Topiramate 200mgDrug
Also called Topamax
Topiramate: 200 mg, po, 1x

Study groups in NCT01889602
Study group	Role	What they receive
Topiramate 100mg	Experimental	Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 100mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments. Receives: Drug: Lorazepam; Other: Placebo; Drug: Topiramate 100mg
Topiramate 150mg	Experimental	Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 150mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments. Receives: Drug: Lorazepam; Other: Placebo; Drug: Topiramate 150mg
Topiramate 200mg	Experimental	Participant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 200mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments. Receives: Drug: Lorazepam; Other: Placebo; Drug: Topiramate 200mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in COWA Unique Word Count
Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Measured: Session 1 to Session 5
Change From Baseline in Spontaneous Narrative Raw Word Count
Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Measured: Session 1 to Session 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Aug 2016

First posted28 Jun 2013 (estimated)
Study startJul 2013
Primary completionAug 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cognitive DeficitsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01889602
Sponsor's protocol ID: CPDEC
Status last verified: Dec 2019
First submitted: 25 Jun 2013
Last updated: 17 Dec 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Callisto SP, Illamola SM, Birnbaum AK, Barkley CM, Bathena SPR, Leppik IE, Marino SE. Severity of Topiramate-Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity. J Clin Pharmacol. 2020 Sep;60(9):1166-1176. doi: 10.1002/jcph.1611. Epub 2020 Apr 16.
PubMed 32297992

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cognitive Deficits trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Characterizing and Predicting Drug Effects on Cognition
ClinicalTrials.gov ID: NCT01889602
Acronym / sponsor ID: CPDEC
Conditions: Cognitive Deficits
Keywords: Healthy volunteers, Topiramate, Neurocognition, Drug-induced cognitive deficits
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: University of MinnesotaUniversity, hospital or other
Study start: Jul 2013
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 28 Jun 2013 (estimated)
Results: Posted 17 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Topiramate 100mg	Experimental	Drug: Lorazepam, Other: Placebo, Drug: Topiramate 100mgParticipant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 100mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.
Topiramate 150mg	Experimental	Drug: Lorazepam, Other: Placebo, Drug: Topiramate 150mgParticipant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 150mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.
Topiramate 200mg	Experimental	Drug: Lorazepam, Other: Placebo, Drug: Topiramate 200mgParticipant will receive 3 single-dose treatments with 2-week washout between each treatment. At each of 3 treatments, participants will receive 200mg torpiramate, 2mg lorazepam, or placebo. Treatment order is randomized. All participants in this arm will receive all 3 treatments.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Healthy men and women
Ages 18-50
Women are post-menopausal or using approved birth control methods
To control for brain lateralization of language functions, subjects need to have a dominant right hand.

Key exclusion criteria (8 listed)

Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, renal, neurologic, and/or psychiatric disease including suicidality
Vision or hearing impairments
Current or a history of drug or alcohol abuse
living outside of the Twin Cities Metropolitan area.
The use of concomitant medications known to affect Topiramate (TPM), Lorazepam (LZP), or the use of any concomitant medications that may alter cognitive function

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LorazepamAlso: AtivanLorazepam: 2mg, po, 1x	Drug	Topiramate 100mg, Topiramate 150mg, Topiramate 200mg
PlaceboNon-active placebo, po, 1x	Other	Topiramate 100mg, Topiramate 150mg, Topiramate 200mg
Topiramate 100mgAlso: TopamaxTopiramate: 100 mg, po, 1x	Drug	Topiramate 100mg
Topiramate 150mgAlso: TopamaxTopiramate: 150 mg, po, 1x	Drug	Topiramate 150mg
Topiramate 200mgAlso: TopamaxTopiramate: 200 mg, po, 1x	Drug	Topiramate 200mg

Primary outcome

Change From Baseline in COWA Unique Word Count
Time frame: Session 1 to Session 5
Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Change From Baseline in Spontaneous Narrative Raw Word Count
Time frame: Session 1 to Session 5
Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.

Results and safety

Results posted to the registry on 17 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Topiramate 100mg	20	19
Topiramate 150mg	20	17
Topiramate 200mg	20	18

Primary outcome: Change From Baseline in COWA Unique Word Count

Time frame: Session 1 to Session 5. Mean (Standard Deviation). Unit: Word Count

Measure	Arm: Topiramate 100mg, Period: Topiramate n = 14	Arm:Topiramate 150mg, Period: Topiramate n = 15	Arm: Topiramate 200mg, Period: Topiramate n = 17	Arm: Topiramate 100mg, Period: Lorazepam n = 14	Arm: Topiramate 150mg, Period: Lorazepam n = 15	Arm: Topiramate 200mg, Period: Lorazepam n = 17	Arm: Topiramate 100mg, Period: Placebo n = 14	Arm: Topiramate 150mg, Period: Placebo n = 15	Arm: Topiramate 200mg, Period: Placebo n = 17
Value	-0.407725385 (0.110593408)	-0.425898667 (0.186240451)	-0.412534118 (0.154640084)	-0.108298333 (0.240452491)	0.131452143 (0.263967943)	-0.095221176 (0.228163172)	-0.011651538 (0.152526619)	0.077431333 (0.176020802)	0.047164706 (0.166162762)

Primary outcome: Change From Baseline in Spontaneous Narrative Raw Word Count

Time frame: Session 1 to Session 5. Mean (Standard Deviation). Unit: Word Count

Measure	Arm: Topiramate 100mg, Period: Topiramate n = 14	Arm:Topiramate 150mg, Period: Topiramate n = 15	Arm: Topiramate 200mg, Period: Topiramate n = 17	Arm: Topiramate 100mg, Period: Lorazepam n = 14	Arm: Topiramate 150mg, Period: Lorazepam n = 15	Arm: Topiramate 200mg, Period: Lorazepam n = 17	Arm: Topiramate 100mg, Period: Placebo n = 14	Arm: Topiramate 150mg, Period: Placebo n = 15	Arm: Topiramate 200mg, Period: Placebo n = 17
Value	-0.01596 (0.360237984)	-0.131732 (0.192165204)	-0.323135625 (0.297067179)	0.109636 (0.236323153)	0.016635385 (0.283748379)	-0.128177333 (0.281246222)	0.117455385 (0.360519103)	-0.01098 (0.272331286)	0.011456471 (0.225720885)

Adverse events

Time frame: 30 days following the last administration of study drug.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Topiramate 100mg	0 of 14 (0%)	0 of 14 (0%)	0 of 14
Topiramate 150mg	0 of 15 (0%)	0 of 15 (0%)	0 of 15
Topiramate 200mg	0 of 17 (0%)	1 of 17 (5.9%)	0 of 17
Lorazepam 2mg	0 of 46 (0%)	0 of 46 (0%)	0 of 46
Placebo	0 of 46 (0%)	0 of 46 (0%)	0 of 46

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32297992Callisto SP, Illamola SM, Birnbaum AK, Barkley CM, Bathena SPR, Leppik IE, Marino SE. Severity of Topiramate-Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity. J Clin Pharmacol. 2020 Sep;60(9):1166-1176. doi: 10.1002/jcph.1611. Epub 2020 Apr 16.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Susan E. Marino, PhD principal investigator

Assistant Professor

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lorazepam, Topiramate 100mg and Topiramate 150mg in people with Cognitive Deficits, run by University of Minnesota at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in COWA Unique Word Count (time frame: Session 1 to Session 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01889602, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019; AzTrials last refreshed its copy on 28 Oct 2026.