Nicotine Effects on Endophenotypes of Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Nadine Petrovsky, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01315002
First received: March 14, 2011
Last updated: January 29, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01315002

Sponsors and Collaborators
University Hospital, Bonn
German Research Foundation
Investigators
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
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

ClinicalTrials.gov processed this record on August 21, 2014