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Completed

NCT Number: NCT00492349

Varenicline Adjunctive Treatment in Schizophrenia

The principal aim of the project is to conduct an off-label adjunctive clinical trial evaluating varenicline as a treatment for core neurobiological and clinical deficits in schizophrenia, in addition to evaluating for smoking cessation in schizophrenia patients.

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Key information

Conditions

Schizophrenia Cognition Disorders Mental Disorders Neurocognitive Disorders Psychotic Disorders Schizoaffective Disorder Schizophrenia Spectrum and Other Psychotic Disorders Schizophreniform Disorder

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Maryland Psychiatric Research Center, Baltimore, Maryland, United States

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About this study

This is a double-blind, placebo controlled clinical trial in schizophrenia patients. Outcome measures include biomarkers and clinical symptoms and functions, and smoking cessation. Neurobiological and cognitive markers will be measured for short term (2 weeks) and longer-term (8 weeks). Current schizophrenia treatments are mostly ineffective against primary negative symptoms and the cognitive and information processing deficits associated with the disorder. Previous research has identified several neurophysiological deficits in schizophrenia that are enduring, frequently occurring before psychosis, and mark the disease liability. These schizophrenia endophenotypes provide important targets for novel treatment development as they represent the core deficits of the disorder. We hypothesize that sustained nicotinic and dopaminergic modulation by varenicline may ameliorate the core neurobiological deficits seen in schizophrenia patients, which would lead to subsequent clinical improvement. Neurobiological and neurocognitive markers and clinical and functional measures will be obtained to determine 1) short-term effect of varenicline on biomarkers; and 2) longer-term improvement in clinical symptoms, smoking cessation, and functions; and how biomarker changes predict these improvements.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-60
  • DSM-IV Diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder
  • Clinically stable with no change in antipsychotic medications and increase of daily dose for 4 weeks prior to enrollment
  • Sufficient understanding of the study and risks (ESC score 10 or above)

Exclusion criteria

  • Major medical illness history including, but not limited to, history of heart attack, stroke, TIA (transient ischemic attack)
  • History of organic brain disorders that may affect neurophysiological measurements, including seizure disorder, brain tumor, head injury with evidence of significant cognitive deterioration
  • DSM-IV diagnosis of substance dependence within 6 months except nicotine and marijuana
  • On nicotine replacement therapy (nicotine patch, gum, or nasal spray)
  • Uncontrolled blood pressure (persistent systolic above 155 or diastolic above 95)
  • EKG of second or third degree atrioventricular (AV) block
  • Renal insufficiency with estimated creatinine clearance <40 ml/min
  • Women who have positive urine pregnancy tests
  • Women who are pregnant, plan to become pregnant, or in breastfeeding

Treatment and study plan

Varenicline

Drug

Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks

Other names: Chantix

Placebo

Drug

Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks

Primary outcomes

  1. Hamilton Depression Rating Scale (Ham-D)

    Time frame: Week 8

    Ham-D Total Score (range 0 to 54, higher score is worse). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  2. Memory Saccadic Positional Error, Degrees

    Time frame: Week 8

    A saccade is a quick eye movement. Spatial working memory was assessed by memory saccade. Participants were asked to focus on a target while a peripheral cue was flashed. Participants were signaled to look in the direction of the peripheral cue when the central target was removed, and the positional error was calculated as the distance between the saccadic and peripheral target positions. Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  3. Predictive Pursuit Gain

    Time frame: Week 8

    Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Participants are asked to track a target with their eyes. Participants may use a predictive mechanism to perform the tracking. The pursuit gain using the predictive mechanism is calculated. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  4. Maintenance Pursuit Gain

    Time frame: Week 8

    Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Eye velocity during the regular eye-tracking period (without foveal stabilization) divided by target velocity was used to calculate the maintenance pursuit gain. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  5. Digit Symbol Test

    Time frame: Week 0, Week 2 and Week 8

    Digit symbol test score (0 to no definite upper range, higher score is better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  6. Conner's Continuous Performance Test (CPT) Detectability Score

    Time frame: Week 0, Week 2 and Week 8

    Conner's CPT Detectability Score (no set normal range, higher is generally better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  7. Antisaccade Error Rates

    Time frame: Week 0, Week 2 and Week 8

    In antisaccade, participants were asked to focus on a central target. When a peripheral cue was presented, participants were asked to look in an equidistant and opposite direction of the peripheral cue. The error rate is calculated as the number of trials in which the participant looked toward the cue, rather than in the opposite direction, divided by the total number of trials. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

  8. P50

    Time frame: Week 0, Week 2 and Week 8

    P50 response is a measure of the amplitude of the brain wave in response to a sound, where the positive going amplitude of the brain wave occurring at about 50 milliseconds after the sound. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Collaborators

  • Stanley Medical Research Institute

Registry information

Important dates

Study start
2007
Primary completion
2010
Study completion
2011
First posted
Jun 27, 2007
Registry last updated
Jan 5, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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