Social Cognition,Attentional Network and Nicotine Drug Dependency - A Pharmacological Clinical Trail (NIKOGEN)

In the present study, we investigate healthy subjects and schizophrenic patients who frequently show very low attentional capacity with functional magnetic resonance imaging (fMRI) and electrophysiology (EEG) during attention-requiring tasks to assess the level of attentional network activity.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Tobacco Use Disorder
• Intervention / Treatment: Drug: nicotine nasal spray

Detailed Description

Nicotine is improving attentional capacity which goes along with an activation of the attentional network in the brain. So far, however, it is unresolved whether nicotine is used for the purpose of self-medication by those nicotine-dependent subjects who suffer from subclinical or clinical attentional deficits which may sustain nicotine addiction. In the present study, we investigate healthy subjects and schizophrenic patients who frequently show very low attentional capacity with functional magnetic resonance imaging (fMRI) and electrophysiology (EEG) during attention-requiring tasks to assess the level of attentional network activity. It is anticipated that low attentional network activity (during baseline condition, after nicotine challenge and after withdrawal) predicts the degree of nicotine dependence including the strength of withdrawal symptoms and relapse rate after smoking cessation. In addition, we expect that functional variations within alpha4beta2 nAch receptor genotype are associated with attentional capacity and -by extension - with nicotine dependence.

Additionally Self-medication of attentional deficits and of increased stress vulnerability may contribute to nicotine-dependence both in schizophrenia patients and healthy subjects. However, very little is known about the effect of nicotine on stress in schizophrenia. In particular social stressors are highly relevant in schizophrenia often resulting in social withdrawal. A factor contributing to the stress-eliciting nature of social interaction is the misidentification of social information during communication with others. The present project aims at an investigation of nicotine effects on such social information processing and its neurophysiological correlates and on social stress responses. Using a 2x2-factorial design effects of nicotine vs. placebo are experimentally investigated in smoking schizophrenia patients in comparison to smoking healthy controls each after an overnight smoking deprivation. Nicotine will be administered by nasal spray delivering a systemic does of 2 mg nicotine. Event-related EEG potentials will be recorded during the presentation of pictures of facial affect and neutral control stimuli to assess social information processing and its neurophysiological correlates. In addition a videotaped semi-standardized conversation skills role-play test will be used as a social stress situation to assess self-reported and non-verbal affective responses.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • NW
    • Duesseldorf, NW, Germany, 40629
      • Psychiatrische Klinik und Poliklinik der Heinrich-Heine-Universität
    • Jülich, NW, Germany, 52425
      • Forschungszentrum Jülich GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-55
• informed consent
• negative drug-screening (cannabis, amphetamine, opiate, cocaine)
• no drug abuse in medical history for last 6 month
• no participation of subjects in other pharmacological trials within 6 weeks
• negative pregnancy test
• use of effective contraception within participation of trial
• normotonia (heart rate, RR)
• nicotine dependence (Fagerström >4)or not more than 20 cigarettes /lifetime
• nicotine (smoker serum > 2ng/mL)
• DSM-IV criteria for schizophrenia
• healthy subjects

Exclusion Criteria:

• known hypersensitivity towards nicotine or any substance of placebo preparation
• adenoids
• Rhinitis vaso.
• hypersensitivity of air passages
• cardiovascular diseases (defined)
• neurological diseases (defined)
• diabetes mellitus
• hyperthyreosis
• phaeochromocytoma
• Clozapine (schizophrenic)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; schizophrenic and non schizophrenic patient stratified by smoking and non smoking will get nicotine and placebo on first day on the second day placebo and nicotine	Drug: nicotine nasal spray; 0,5 mg nicotine nasal spray or placebo (pepperspray); Other Names: nicorette nasal spray
Placebo Comparator: 2; schizophrenic and non schizophrenic patient stratified by smoking and non smoking will get nicotine and placebo on first day on the second day placebo and nicotine	Drug: nicotine nasal spray; 0,5 mg nicotine nasal spray or placebo (pepperspray); Other Names: nicorette nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of nicotine or placebo in healthy subjects and schizophrenic patients on attentional network activity in brain with functional magnetic resonance imaging and EEG	after last subject out

Secondary Outcome Measures

Outcome Measure	Time Frame
-Effect of nicotine on a4b2 nAch receptor genotype -Gene Expression of a4b2 nAch -effect of 24 h nicotine withdrawal on modulation special hormones -effect of nicotine on neurophysiological correlates of social stress	after last subject out

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: G. Winterer, Prof. Dr., Department of Psychiatry and Psychotherapy

Publications and helpful links

General Publications

• Warbrick T, Mobascher A, Brinkmeyer J, Musso F, Stoecker T, Shah NJ, Fink GR, Winterer G. Nicotine effects on brain function during a visual oddball task: a comparison between conventional and EEG-informed fMRI analysis. J Cogn Neurosci. 2012 Aug;24(8):1682-94. doi: 10.1162/jocn_a_00236. Epub 2012 Mar 27.
• Luckhaus C, Henning U, Ferrea S, Musso F, Mobascher A, Winterer G. Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased in schizophrenia and correlates with negative symptoms. J Neural Transm (Vienna). 2012 May;119(5):587-95. doi: 10.1007/s00702-011-0743-1. Epub 2011 Dec 11.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: February 8, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (Estimate): February 20, 2008

Study Record Updates

• Last Update Posted (Estimate): March 2, 2012
• Last Update Submitted That Met QC Criteria: March 1, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: NIKOGEN_HHU_2006