Characterizing and Predicting Drug Effects on Cognition
Condition: Cognitive Deficits
MeSH terms: Cognition Disorders; Cognitive Dysfunction
Intervention: Lorazepam; Placebo; Topiramate 100mg; Topiramate 150mg; Topiramate 200mg
Intervention description: Lorazepam: 2mg, po, 1x; Non-active placebo, po, 1x; Topiramate: 100 mg, po, 1x; Topiramate: 150 mg, po, 1x; Topiramate: 200 mg, po, 1x
Intervention MeSH terms: Topiramate; Lorazepam
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy volunteers; Topiramate; Neurocognition; Drug-induced cognitive deficits

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.
    

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