Nicotine Effects on Endophenotypes of Schizophrenia

January 7, 2015 updated by: Nadine Petrovsky, University Hospital, Bonn
The purpose of this study is to test the effects of nicotine on cognition with the following schizophrenia endophenotypes: prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Schizophrenia patients, unaffected first-degree relatives of schizophrenia patients and healthy controls receive transdermal nicotine in a double-blind, placebo-controlled, crossover study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Convergent findings suggest that an altered neuronal nicotinic acetylcholine receptor system may contribute to the pathophysiology of schizophrenia. Nicotine consumption through cigarette smoking might represent a form of self-medication in schizophrenia as nicotine reduces cognitive and physiological deficits in schizophrenia. The present study aims to investigate how nicotine affects attentional and executive schizophrenia endophenotypes and how genetic polymorphisms relating to the cholinergic system might play a role in inter-individual differences in the magnitude of nicotine effects.

Schizophrenia patients, first-degree relatives of schizophrenia patients as well as healthy controls will receive transdermal nicotine in a double-blind, placebo-controlled, crossover study and will be assessed with prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Subjects will be overnight-abstinent smokers and non-smokers. However, the investigators will particularly test non-smokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement.

Main hypotheses:

  • Schizophrenia patients will perform worse than matched controls in all cognitive tests (validating our endophenotypes).
  • Nicotine administration will enhance cognitive performance in overnight-abstinent smokers.
  • Improvement of cognitive performance in smokers with schizophrenia will be stronger than in control smokers.
  • Improvement of cognitive performance in smoking first-degree relatives of schizophrenia patients will be stronger than in control smokers.
  • Nicotine administration will affect cognitive functioning in non-smoking subjects.
  • Nicotine administration will improve cognitive functioning in non-smoking schizophrenia patients.
  • The effects of nicotine in non-smoking subjects are stronger in those subjects who are cognitively more impaired (i.e. performing below the median of the respective group).

The present research contributes to the issue whether nicotinic cholinergic receptor agonists may have therapeutic value in the treatment of cognition in schizophrenia.

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Not Applicable

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:

Patients:

  • Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) diagnosis of schizophrenia
  • age 18-55 years old
  • able to provide informed consent
  • treated with antipsychotic medications at a stable dose for at least 6 weeks
  • normal or corrected to normal vision
  • smokers (Fagerström Test for Nicotine Dependence > 4)
  • non-smokers (< 100 cigarettes/lifetime, not having smoked in the past year)

Controls:

  • age 18-55 years old
  • able to provide informed consent
  • normal or corrected to normal vision
  • smokers (Fagerström Test for Nicotine Dependence > 4)
  • non-smokers (< 100 cigarettes/lifetime, not having smoked in the past year)

Unaffected First-Degree Relatives of Schizophrenia Patients:

  • same inclusion criteria as controls plus
  • having an adult first-degree relative (sibling, parent, child) with a DSM IV diagnosis of schizophrenia

Exclusion Criteria:

Patients:

  • substance dependence
  • clinical instability
  • changes in medication in the last 6 weeks
  • anticholinergic medication
  • untreated hypertension
  • cardiovascular disease
  • insulin-dependent diabetes mellitus
  • phaeochromocytoma
  • uncontrolled hyperthyroidism
  • renal or hepatic impairment
  • central nervous system disease
  • pulmonary disease
  • generalised dermatological disorders (neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
  • gastric or intestinal ulcer
  • hypersensitivity to nicotine
  • allergy to patches
  • women: pregnancy, lactation

Controls:

  • substance dependence
  • having a first-, second-, or third-degree relative with a psychotic disorder
  • DSM IV Axis I disorder
  • anticholinergic medication
  • untreated hypertension
  • cardiovascular disease
  • insulin-dependent diabetes mellitus
  • phaeochromocytoma
  • uncontrolled hyperthyroidism
  • renal or hepatic impairment
  • central nervous system disease
  • pulmonary disease
  • generalised dermatological disorders (neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
  • gastric or intestinal ulcer
  • hypersensitivity to nicotine
  • allergy to patches
  • women: pregnancy, lactation

Unaffected First-Degree Relatives of Schizophrenia Patients:

  • same exclusion criteria as controls

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nicotine Patch
Transdermal nicotine patch
Drug: Transdermal nicotine patch
7mg transdermal nicotine patch (non-smoking subjects) 14mg transdermal nicotine patch (smoking subjects)
Other Names:
  • NiQuitin Clear, GlaxoSmithKline Germany
Placebo Comparator: Placebo patch
Drug: Placebo patch
Placebo patch
Other Names:
  • band-aid by Fink and Walter GmbH, Germany

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Error Percentage in Antisaccade Task
Time Frame: Three hours after patch application
Three hours after the application of a nicotine or a placebo patch, performance on the antisaccade task is assessed. In the antisaccade task participants visually fixate a central stimulus which is replaced by a sudden onset target that appears at some distance to the left or right. Participants are told to refrain from looking at the peripheral target, and direct their gaze instead in the opposite direction (i.e. they have to make an antisaccade). Participants typically fail to achieve this on a significant number of trials and instead make reflexive glances towards the target (i.e. making a so-called antisaccade error). Error percentage in the antisaccade task is the unit of measure in this task. Error percentage in the antisaccade task = number of antisaccade errors / total number of trials.
Three hours after patch application

Collaborators and Investigators

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

Sponsor

University Hospital, Bonn

Collaborators

German Research Foundation

Investigators

  • Principal Investigator: Michael Wagner, Prof. Dr., University Hospital, Bonn
  • Principal Investigator: Wolfgang Maier, Prof. Dr., University Hospital, Bonn

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

July 1, 2008

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

March 14, 2011

First Submitted That Met QC Criteria

March 14, 2011

First Posted (Estimate)

March 15, 2011

Study Record Updates

Last Update Posted (Estimate)

January 16, 2015

Last Update Submitted That Met QC Criteria

January 7, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NICSZ001
  • 2008-001362-90 (EudraCT Number)

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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