Characterizing and Predicting Drug Effects on Cognition
Condition: Cognitive Deficits
MeSH terms: Cognition Disorders; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Lorazepam; Placebo; Topiramate 100mg; Topiramate 150mg; Topiramate 200mg
Intervention type(s): Drug; Other; Drug; Drug; Drug
Intervention description(s): Lorazepam: 2mg, po, 1x; Non-active placebo, po, 1x; Topiramate: 100 mg, po, 1x; Topiramate: 150 mg, po, 1x; Topiramate: 200 mg, po, 1x
Other intervention name(s): Ativan; Topamax; Topamax; Topamax
Intervention MeSH terms: Topiramate; Lorazepam
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Healthy volunteers; Topiramate; Neurocognition; Drug-induced cognitive deficits