Varenicline Adjunctive Treatment in Schizophrenia

January 3, 2022 updated by: L. Elliot Hong, University of Maryland, Baltimore
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

91

Phase

  • Phase 4

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

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21228
        • Maryland Psychiatric Research Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical System
      • Baltimore, Maryland, United States, 21201
        • UMB School of Medicine

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 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Placebo
Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks
Experimental: 1
Varenicline
Drug: Varenicline
Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks
Other Names:
  • Chantix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 8
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.
Week 8
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.
Week 8
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.
Week 8
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.
Week 0, Week 2 and Week 8
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.
Week 0, Week 2 and Week 8
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.
Week 0, Week 2 and Week 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.
Week 0, Week 2 and Week 8

Collaborators and Investigators

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

Sponsor

University of Maryland, Baltimore

Collaborators

Stanley Medical Research Institute

Investigators

  • Principal Investigator: L. Elliot Hong, M.D., Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine

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.

General Publications

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

May 1, 2007

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

June 26, 2007

First Submitted That Met QC Criteria

June 26, 2007

First Posted (Estimate)

June 27, 2007

Study Record Updates

Last Update Posted (Actual)

January 5, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00040322

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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