Nicotine Effects on Endophenotypes of Schizophrenia

Schizophrenia Clinical Trial

Official title:

Nicotine Effects on Endophenotypes of Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01315002
• Other study ID #: NICSZ001
• Secondary ID: 2008-001362-90
• Status: Completed
• Phase: N/A
• First received: March 14, 2011
• Last updated: January 7, 2015
• Start date: July 2008
• Est. completion date: March 2012

Study information

• Verified date: January 2015
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Transdermal nicotine patch
7mg transdermal nicotine patch (non-smoking subjects) 14mg transdermal nicotine patch (smoking subjects)
• Placebo patch
Placebo patch

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bonn	German Research Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Three hours after patch application	No