Nicotine Effects on Endophenotypes of Schizophrenia
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Schizophrenia |
Drug: Transdermal nicotine patch Drug: Placebo patch |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science |
| Official Title: | Nicotine Effects on Endophenotypes of Schizophrenia |
- Change in cognitive functioning [ Time Frame: Three hours after patch application ] [ Designated as safety issue: No ]About three hours after the application of a nicotine/placebo patch, the change in cognitive functioning is assessed. The cognitive functions being assessed include prepulse inhibition, antisaccade eye movements, the continuous performance task, spatial working memory, and a verbal memory task.
- Change in cognitive functioning as a function of genotype [ Time Frame: Three hours after patch application ] [ Designated as safety issue: No ]It will be assessed whether there is an association between nicotine-induced changes in cognitive functioning and polymorphisms in the nicotinic acetylcholine receptor genes.
| Enrollment: | 121 |
| Study Start Date: | July 2008 |
| Study Completion Date: | March 2012 |
| Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Name: NiQuitin Clear, GlaxoSmithKline Germany
|
|
Placebo Comparator: Placebo patch
Placebo patch
|
Drug: Placebo patch
Placebo patch
Other Name: band-aid by Fink and Walter GmbH, Germany
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations| Principal Investigator: | Michael Wagner, Prof. Dr. | University Hospital, Bonn |
| Principal Investigator: | Wolfgang Maier, Prof. Dr. | University Hospital, Bonn |
More Information
No publications provided
| Responsible Party: | Nadine Petrovsky, PhD, University Hospital, Bonn |
| ClinicalTrials.gov Identifier: | NCT01315002 History of Changes |
| Other Study ID Numbers: | NICSZ001, 2008-001362-90 |
| Study First Received: | March 14, 2011 |
| Last Updated: | January 29, 2013 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by University Hospital, Bonn:
|
nicotine schizophrenia endophenotype |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia and Disorders with Psychotic Features Mental Disorders Nicotine Nicotine polacrilex Ganglionic Stimulants Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
Pharmacologic Actions Nicotinic Agonists Cholinergic Agonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Central Nervous System Stimulants Central Nervous System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 19, 2013