Effects of Varenicline on Plasticity in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      This laboratory pilot study will explore the effects of varenicline tartrate on long-term
      potentiation (LTP)-like mechanisms of (1) the motor cortex and (2) the dorsolateral
      prefrontal cortex (DLPFC) and working memory in non-smoking patients with schizophrenia and
      healthy controls using a Paired Associative Stimulation (PAS) method. The present study will
      use this novel PAS method to evaluate the effects of five doses of varenicline (Champix) 0.5
      mg BID treatment on neuroplasticity changes and working memory in 28 non-smokers with
      schizophrenia and 28 non-smoking controls in a placebo-controlled, double-blinded, cross-over
      design. The hypothesis is that varenicline will increase LTP-like facilitation of the DLPFC
      as compared with placebo in patients with schizophrenia, with less or a null effect in
      healthy controls. Likewise, it is hypothesized that varenicline will specifically improve
      working memory in patients with schizophrenia as compared with placebo and healthy controls.
      We Hypothesize that: 1.Patients with Schizophrenia(SCZ) will have reduced cortical LTP and
      impaired working memory compared to healthy controls 2. Sub-chronic varenicline challenge
      will attenuate the cortical LTP and working memory deficit in patients with SCZ. 3.Reversal
      of the cortical LTP deficit by varenicline in patients with SCZ will be associated with
      improvement in working memory.
    

Detailed description: 
      The experimental laboratory study will be designed as a randomized, double-blinded,
      placebo-controlled acute treatment trial. Paired Associative Stimulation (PAS)-induced
      cortical evoked activity and Working Memory (WM) will be assessed in healthy non-smokers and
      non-smokers with SCZ, after five doses of varenicline tartrate (0.5 mg/dose) and placebo
      treatment. PAS will be induced by pairing transcranial magnetic stimulation with peripheral
      nerve stimulation, 25 msec apart (hence PAS-25). In part 1, motor cortex plasticity will be
      assessed as changes in motor evoked potential comparing pre to post PAS up tp 120 min after
      PAS. In part 2, DLPFC evoked cortical activity will be assessed using EEG comparing pre to
      post PAS. Effects of varenicline and PAS-25 on WM will evaluated using a computerized N-back
      task, assessed directly before the PAS testing. The whole experimental session will be
      repeated for each participant twice: once with varenicline tartrate treatment and once with
      placebo treatment, two weeks apart.
    

Intervention name(s): Varenicline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Champix (Varenicline) is an approved smoking cessation medication
Other intervention name(s): Champix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Keywords: plasticity, schizophrenia, varenicline, non smokers,