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

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ClinicalTrials.gov Identifier: NCT01934023
Recruitment Status : Completed
First Posted : September 4, 2013
Last Update Posted : August 25, 2015
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Tony George, Centre for Addiction and Mental Health

Brief 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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Varenicline Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Official Title: Effects of Varenicline on Cortical Neuroplasticity and Working Memory in Patients With Schizophrenia and Healthy Controls
Study Start Date : September 2013
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory Schizophrenia

Arm Intervention/treatment
Active Comparator: Varenicline
FDA approved smoking cessation medication
Drug: Varenicline
Champix (Varenicline) is an approved smoking cessation medication
Other Name: Champix

Placebo Comparator: Placebo Sugar Pill
sugar pill
Drug: Placebo



Primary Outcome Measures :
  1. Change of Paired Associative Stimulation (PAS) induced plasticity from baseline [ Time Frame: Day 3 of weeks 1 and 2 ]

Secondary Outcome Measures :
  1. Change of Working memory performance from baseline [ Time Frame: Day 3 of weeks 1 and 2 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01934023


Locations
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Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Pfizer
Investigators
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Principal Investigator: Tony P George, M.D Centre for Addiction Mental Health

Additional Information:
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Responsible Party: Tony George, Chief, Schizophrenia Division, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01934023     History of Changes
Other Study ID Numbers: 214-2012
Wi172662 ( Other Grant/Funding Number: Pfizer )
First Posted: September 4, 2013    Key Record Dates
Last Update Posted: August 25, 2015
Last Verified: August 2015
Keywords provided by Tony George, Centre for Addiction and Mental Health:
plasticity, schizophrenia, varenicline, non smokers,
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs