Effects of Varenicline on Plasticity in Schizophrenia (VAR-PAS)

August 24, 2015 updated by: Tony George, Centre for Addiction and Mental Health

Effects of Varenicline on Cortical Neuroplasticity and Working Memory in Patients With Schizophrenia and Healthy Controls

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 1R8
        • Centre for Addiction and Mental Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria (Healthy subjects and Scz):

  • Non-smoker or past smoker, abstinent for at least the last 1 year
  • Females with potential childbearing must have a negative serum pregnancy test at inclusion.
  • Ability and willingness to speak English
  • Willingness to provide informed consent
  • Adequate hearing and visual capacity, or corrected by visual/ hearing aid, right handedness.

INCLUSION Criteria (Scz Only):

  • Diagnosis of schizophrenia
  • Stable psychotropic drug treatment for at least the past 4 weeks
  • Clinically stable for the past 3 months.

Exclusion Criteria (healthy subjects and SCZ):

  • Current smoker or abstinent smoker for less than 1 year
  • Current history of drug abuse disorder or current elicit drug use
  • Current or past history of neurological disorder
  • Current or past history of seizures
  • Any metal implants
  • Mini Mental Status Examination score of less than 20
  • Diagnosis of bipolar disorder or current Major depression episode
  • Electroconvulsive Therapy (ECT) within 6 months
  • Varenicline hypersensitivity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Varenicline
FDA approved smoking cessation medication
Drug: Varenicline
Champix (Varenicline) is an approved smoking cessation medication
Other Names:
  • Champix
Placebo Comparator: Placebo Sugar Pill
sugar pill
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change of Paired Associative Stimulation (PAS) induced plasticity from baseline
Time Frame: Day 3 of weeks 1 and 2
Day 3 of weeks 1 and 2

Secondary Outcome Measures

Outcome Measure
Time Frame
Change of Working memory performance from baseline
Time Frame: Day 3 of weeks 1 and 2
Day 3 of weeks 1 and 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Collaborators

Pfizer

Investigators

  • Principal Investigator: Tony P George, M.D, Centre for Addiction Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

August 27, 2013

First Submitted That Met QC Criteria

September 3, 2013

First Posted (Estimate)

September 4, 2013

Study Record Updates

Last Update Posted (Estimate)

August 25, 2015

Last Update Submitted That Met QC Criteria

August 24, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 214-2012
  • Wi172662 (Other Grant/Funding Number: Pfizer)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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