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Nicotine Effects on Endophenotypes of Schizophrenia

Primary Purpose

Schizophrenia

Status

Completed

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Transdermal nicotine patch

Placebo patch

About this trial

This is an interventional basic science trial for Schizophrenia focused on measuring nicotine, schizophrenia, endophenotype

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nicotine Patch

Placebo patch

Arm Description

Transdermal nicotine patch

Placebo patch

Outcomes

Primary Outcome Measures

Error Percentage in Antisaccade Task

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01315002

First Posted

March 14, 2011

Last Updated

January 7, 2015

Sponsor

University Hospital, Bonn

Collaborators

German Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01315002

Brief Title

Nicotine Effects on Endophenotypes of Schizophrenia

Official Title

Nicotine Effects on Endophenotypes of Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Bonn

Collaborators

German Research Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

Keywords

nicotine, schizophrenia, endophenotype

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

121 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nicotine Patch

Arm Type

Active Comparator

Arm Description

Transdermal nicotine patch

Arm Title

Placebo patch

Arm Type

Placebo Comparator

Arm Description

Placebo patch

Intervention Type

Drug

Intervention Name(s)

Transdermal nicotine patch

Other Intervention Name(s)

NiQuitin Clear, GlaxoSmithKline Germany

Intervention Description

7mg transdermal nicotine patch (non-smoking subjects) 14mg transdermal nicotine patch (smoking subjects)

Intervention Type

Drug

Intervention Name(s)

Placebo patch

Other Intervention Name(s)

band-aid by Fink and Walter GmbH, Germany

Intervention Description

Placebo patch

Primary Outcome Measure Information:

Title

Error Percentage in Antisaccade Task

Description

Time Frame

Three hours after patch application

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Wagner, Prof. Dr.

Organizational Affiliation

University Hospital, Bonn

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Wolfgang Maier, Prof. Dr.

Organizational Affiliation

University Hospital, Bonn

Official's Role

Principal Investigator

12. IPD Sharing Statement

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Nicotine Effects on Endophenotypes of Schizophrenia

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