Neural Inhibition as a Mechanism of Nicotine Dependence Among Persons With Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Canadian Psychiatric Research Foundation
Information provided by:
Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT00407277
First received: November 30, 2006
Last updated: March 17, 2009
Last verified: March 2009
  Purpose

Cigarette smoking decreases life expectancy, causes devastating health complications, and costs society billions of dollars each year. These untoward consequences are especially pronounced among persons with schizophrenia (SCZ) because approximately 80% to 95% of this group smokes cigarettes. These high prevalence rates underscore the need for research investigating the determinants of smoking in patients with SCZ. Several researchers have observed that nicotine improves specific symptoms of SCZ including negative symptoms, negative affect, and cognitive deficits. This has led to the hypothesis that patients with SCZ smoke in an attempt to self-medicate. However, the mechanism(s) by which nicotine has its positive effect on symptoms remains unclear. The current proposal posits that neural inhibition (NI) is a physiological mechanism of this effect, while variation in the alpha-7-nicotinic receptor subunit gene (CHRNA7) represents the genetic underpinnings of these processes. The proposed study will assess NI and symptom improvement after acute administration of nicotine to both smokers and nonsmokers with SCZ. In addition, NI and CHRNA7 variation will be tested as predictors of patients' ability to reduce/quit smoking following smoking treatment. These data may lead to the development of new pharmacological strategies for treating the symptoms of SCZ and new methods for assisting these patients to quit smoking.


Condition Intervention
Smoking
Nicotine Dependence
Schizophrenia
Schizophreniform Disorders
Schizoaffective Disorder
Psychosis
Drug: Nicotine patch
Other: placebo
Behavioral: smoking cessation group therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Neural Inhibition as a Mechanism of Nicotine Dependence Among Persons With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • neural inhibition via EEG and TMS [ Time Frame: intermittent ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Self reported tobacco use [ Time Frame: intermittent ] [ Designated as safety issue: No ]
  • Polymorphic markers in the CHRNA7 gene and promoter region [ Time Frame: baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: February 2007
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1A Drug: Nicotine patch
21 mg of nicotine via a dermal patch
Placebo Comparator: 1B Other: placebo
placebo via a dermal patch
Experimental: 2A Behavioral: smoking cessation group therapy
a 9-week group based on the "Freedom From Smoking" program designed by the American Lung Association. The treatment was manualized and modified to meet the functional and cognitive capabilities of patients with psychotic disorders

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Voluntary and competent to consent
  • Have a diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder as confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV)
  • Between the ages of 18 and 60

Exclusion Criteria:

  • Have a DSM-IV history of substance abuse or dependence (other than caffeine or nicotine) in the last 6 months
  • Have a self-reported concomitant major medical or neurologic illness
  • Pregnant
  • Currently prescribed medications known to deleteriously affect cognition (e.g., benzodiazepines, tricyclic anti-depressants, anticholinergics, MAO inhibitors, GABA-B agonists)
  • Currently taking clozapine (due to its documented effect on both NI and smoking
  • Report suffering from conditions that may be aggravated by acute nicotine administration (e.g., arrhythmias, recent myocardial infarction)
  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: NCT00407277

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Canadian Psychiatric Research Foundation
Investigators
Principal Investigator: Jeff Daskalakis, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Jeff Daskalakis, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT00407277     History of Changes
Other Study ID Numbers: 63/2005
Study First Received: November 30, 2006
Last Updated: March 17, 2009
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
nicotine dependence
smoking
nicotine patch
double-blind
randomized
placebo
psychosis
schizophrenia
schizophreniform
schizoaffective disorder

Additional relevant MeSH terms:
Schizophrenia
Disease
Psychotic Disorders
Tobacco Use Disorder
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Pathologic Processes
Substance-Related Disorders
Chemically-Induced 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 September 30, 2014