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Characterizing and Predicting Drug Effects on Cognition

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01889602
Recruitment Status : Completed
First Posted : June 28, 2013
Results First Posted : December 17, 2019
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cognitive Deficits Drug: Lorazepam Other: Placebo Drug: Topiramate 100mg Drug: Topiramate 150mg Drug: Topiramate 200mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Characterizing and Predicting Drug Effects on Cognition
Study Start Date : July 2013
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Topiramate 100mg
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.
Drug: Lorazepam
Lorazepam: 2mg, po, 1x
Other Name: Ativan

Other: Placebo
Non-active placebo, po, 1x

Drug: Topiramate 100mg
Topiramate: 100 mg, po, 1x
Other Name: Topamax

Experimental: Topiramate 150mg
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.
Drug: Lorazepam
Lorazepam: 2mg, po, 1x
Other Name: Ativan

Other: Placebo
Non-active placebo, po, 1x

Drug: Topiramate 150mg
Topiramate: 150 mg, po, 1x
Other Name: Topamax

Experimental: Topiramate 200mg
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.
Drug: Lorazepam
Lorazepam: 2mg, po, 1x
Other Name: Ativan

Other: Placebo
Non-active placebo, po, 1x

Drug: Topiramate 200mg
Topiramate: 200 mg, po, 1x
Other Name: Topamax




Primary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01889602


Locations
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United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55414
Sponsors and Collaborators
University of Minnesota
Investigators
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Principal Investigator: Susan E. Marino, PhD Assistant Professor
  Study Documents (Full-Text)

Documents provided by University of Minnesota:
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT01889602    
Other Study ID Numbers: CPDEC
First Posted: June 28, 2013    Key Record Dates
Results First Posted: December 17, 2019
Last Update Posted: December 17, 2019
Last Verified: December 2019
Keywords provided by University of Minnesota:
Healthy volunteers
Topiramate
Neurocognition
Drug-induced cognitive deficits
Additional relevant MeSH terms:
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Cognition Disorders
Cognitive Dysfunction
Neurocognitive Disorders
Mental Disorders
Topiramate
Lorazepam
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action