Characterizing and Predicting Drug Effects on Cognition

Cognitive Deficits Clinical Trial

Official title:

Characterizing and Predicting Drug Effects on Cognition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889602
• Other study ID #: CPDEC
• Status: Completed
• Phase: Phase 4
• Start date: July 2013
• Est. completion date: August 2016

Study information

• Verified date: December 2019
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Deficits
• Cognitive Dysfunction

Intervention

Drug:
• Lorazepam
Lorazepam: 2mg, po, 1x

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

Drug:
• Topiramate 100mg
Topiramate: 100 mg, po, 1x
• Topiramate 150mg
Topiramate: 150 mg, po, 1x
• Topiramate 200mg
Topiramate: 200 mg, po, 1x

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Session 1 to Session 5
Primary	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.	Session 1 to Session 5