Characterizing and Predicting Drug Effects on Cognition | RxWiki

Characterizing and Predicting Drug Effects on Cognition

Overview[ - collapse ][ - ]

Purpose	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	Cognitive Deficits
Intervention	Drug: Topiramate Drug: Lorazepam
Phase	Phase 4
Sponsor	University of Minnesota - Clinical and Translational Science Institute
Responsible Party	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier	NCT01889602
First Received	June 25, 2013
Last Updated	January 10, 2014
Last verified	January 2014

Tracking Information[ + expand ][ + ]

First Received Date	June 25, 2013
Last Updated Date	January 10, 2014
Start Date	July 2013
Estimated Primary Completion Date	May 2017
Current Primary Outcome Measures	Relationship between neurocognitive performance and study drug plasma concentration [Time Frame: up through 96 hours after dose] [Designated as safety issue: No]Plasma concentrations of study drug will be determined at 0, 0.5, 1.5, 2.5, 4, 6, and either 24, 48, 72 or 96 hours after dose. Neurocognitive assessments will be performed at 0.5, 2.5, and 6 hours after dose, and at either 24, 48, 72 or 96 hours after dose.
Current Secondary Outcome Measures	Neurophysiological effect of study drug on working memory [Time Frame: 2.5 hours after dose] [Designated as safety issue: No]Subjects will perform a verbal working memory task while having their EEG recorded.

Descriptive Information[ + expand ][ + ]

Brief Title	Characterizing and Predicting Drug Effects on Cognition
Official Title	Characterizing and Predicting Drug Effects on Cognition
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.
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.
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Condition	Cognitive Deficits
Intervention	Drug: Topiramate Topiramate: 100 mg, 150 mg or 200 mg, po, 1x Other Names: TopamaxDrug: Lorazepam Lorazepam: 2mg, po, 1x Other Names: Ativan
Study Arm (s)	Experimental: Topiramate Topiramate; 100mg, 150 mg or 200 mg, po,1x Active Comparator: Lorazepam Lorazepam: 2mg, po,1x Placebo Comparator: Placebo Placebo: one tablet, po,1x

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	72
Estimated Completion Date	May 2017
Estimated Primary Completion Date	May 2017
Eligibility 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Contact: Susan E Marino, PhD 612-624-2964 marin007@umn.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01889602
Other Study ID Numbers	CPDEC
Has Data Monitoring Committee	Yes
Information Provided By	University of Minnesota - Clinical and Translational Science Institute
Study Sponsor	University of Minnesota - Clinical and Translational Science Institute
Collaborators	Not Provided
Investigators	Principal Investigator: Susan E. Marino, PhD Assistant Professor
Verification Date	January 2014

Locations[ + expand ][ + ]