NCT01889602

Characterizing and Predicting Drug Effects on Cognition

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

Conditions

• Cognitive Deficits

Interventions

Type	Name	Description
DRUG	Lorazepam	Lorazepam: 2mg, po, 1x
OTHER	Placebo	Non-active placebo, po, 1x
DRUG	Topiramate 100mg	Topiramate: 100 mg, po, 1x
DRUG	Topiramate 150mg	Topiramate: 150 mg, po, 1x
DRUG	Topiramate 200mg	Topiramate: 200 mg, po, 1x

Timeline

• Start date: 2013-07-01
• Primary completion: 2016-08-01
• Completion: 2016-08-01
• First posted: 2013-06-28
• Last updated: 2019-12-17
• Results posted: 2019-12-17

Locations

1 site across 1 country: United States