Effects of Acute Nicotine Treatment on Neuroplasticity and Memory in Patients With Schizophrenia (NIC-PAS)

This study has been terminated.
(Limited staff and operating resources)
Sponsor:
Information provided by (Responsible Party):
Tony George, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01465074
First received: November 1, 2011
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

Patients with schizophrenia display cognitive impairments, such as reduced attention and problems with memory. Available medications for schizophrenia poorly alleviate memory problems however, research indicates that nicotine improves memory. In order for there to be memories formed, there has to be changes (neuroplasticity changes) in how the brain cells communicate. One way to induce such changes is by using Transcranial Magnetic Stimulation (TMS) combined with peripheral nerve stimulation in a Paired Associative Stimulation (PAS) paradigm. The investigators laboratory has developed a novel method that measures memory-like brain changes using electroencephalography (EEG), TMS and PAS. The present study will use this novel method to evaluate the effects of acute nicotine gum (4mg) and placebo (regular) gum on memory and memory-like brain changes in schizophrenia and healthy controls. The hypothesis is that nicotine will improve memory and facilitate neuroplasticity changes in the prefrontal cortex of patients with schizophrenia to a larger extent than in healthy controls.


Condition Intervention
Schizophrenia
Drug: Nicotine polacrilex
Drug: Regular chewing gum; Dentyne Ice, Wrigely´s Mint Gum

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Acute Nicotine on Long-term Potentiation in the Dorsolateral Prefrontal Cortex of Patients With Schizophrenia and Healthy Controls

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in prefrontocortical neuroplasticity [ Time Frame: 0, 15, 30, 60, 120 min, 7 days post treatment ] [ Designated as safety issue: No ]
    Change in cortical evoked activity (using EEG) from baseline to the different time points following paired associative stimulation.


Secondary Outcome Measures:
  • Change in working memory [ Time Frame: baseline, 30 and 120 min and 7 days post treatment ] [ Designated as safety issue: No ]

    N-back performance can be assessed in four conditions, where 0-back is the control condition in which the test subject responds to every letter that appears on the screen, making sure the person can respond to the stimuli as it requires no on-line retention of information. The 1, 2 and 3 back conditions assess on-line retention with increasing difficulty. Average performance, i.e. number of accurate responses as well as response time, will be used as outcome measures.

    PAS-NBACK=(Average performance Post-PAS/ Average performance at baseline)*100



Enrollment: 20
Study Start Date: November 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nicotine gum (4 mg)
Nicotine gum will be given once on one of the two test days in a randomized, double-blinded fashion. Gum will be chewed for 30 min before the plasticity induction occurs.
Drug: Nicotine polacrilex
4 mg
Other Name: Nicorette, Extreme Chill
Placebo Comparator: Regular Mint Gum
Regular, taste-, texture- and color matched with the Nicotine Gum will be ingested once on one of the two testing days, 30 min before plasticity induction.
Drug: Regular chewing gum; Dentyne Ice, Wrigely´s Mint Gum
30 min chewing, one dose

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Age of 18-55 years
  • Non-smoker or past smoker, abstinent for at least the last 1 year, non-smoking status will be assessed on the test days by saliva cotinine levels <15ng/mL and exhalation CO levels <10ppm.
  • Females with potential childbearing must have a negative urine pregnancy test at inclusion.
  • Women with child-bearing potential must use contraceptives during the trial Acceptable means of contraception are hormonal methods (pill, injection, vaginal ring), male or female condom, abstinence, injectable contraceptives, intrauterine devices or abstinence.
  • Ability and willingness to speak English
  • Willingness to provide informed consent
  • Adequate hearing and visual capacity, or corrected by visual/ hearing aid • Right handedness

Patients with schizophrenia:

  • Current diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV TR criteria
  • Stable antipsychotic treatment or dosage for the past 4 weeks prior to study entry
  • Clinically stable, i.e. no psychotic episode that required hospitalization within the last 3 months prior to study inclusion

Exclusion Criteria:

General

  • Current smoker or abstinent smoker for less than 1 year
  • Past or current history of drug abuse disorder or current elicit drug use, positive urine drug screen (for any other drug besides benzodiazepines) on any of the two test days
  • Current or past history of neurological disorder, i.e. meets criteria for a cognitive disorder secondary to a neurological or other medical disorder affecting the central nervous system (such as, traumatic brain injury, stroke, Parkinson).
  • Current or past history of seizures
  • Any metal implants
  • Mini Mental Status Examination score of ≤17
  • Diagnosis of bipolar disorder or current major depressive episode
  • Electroconvulsive Therapy (ECT) within 6 months prior to study participation
  • Allergy to any of the following: nicotine resin, xylitol, butylhydroxythyolen E 321, sodium carbonate, corn starch, magnesium oxide, D&C Yellow No 10, menthol, acesulfam potassium, wax, titan oxide, maltitol, sorbitol, gum base, sucralose, palm oil, mannitol, glycerin, calcium carbonate, gum arabic.
  • Any of the following; breast feeding, immediate post-myocardial infarction period, life-threatening arrhythmias, angina pectoris, and active temporomandibular joint disease, oral or pharyngeal inflammation, or history of esophagitis or peptic ulcer.

Healthy controls:

  • Any psychiatric diagnosis except for simple phobias or an adjustment disorder as diagnosed by DSM IV TR
  • Psychotropic medication (except for sedative /hypnotics at a stable dose for at least 4 weeks).
  • Sedative /hypnotics at a stable dose less than 4 weeks
  • A first-degree relative with as past or present history of primary psychotic disorder
  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: NCT01465074

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Tony P George, M.D. Centre for Addiction and Mental Health, Schizophrenia Program, Toronto, ON, Canada
Principal Investigator: Jeff Z Daskalakis, M.D., Ph.D. Centre for Addiction and Mental Health, Brain Stimulation Lab, Toronto, ON, Canada
  More Information

Additional Information:
Publications:
Wing VC, Sacco KA, George TP (2011) Spatial working memory impairments induced by cigarette smoking abstinence are correlated with plasma nicotine levels in schizophrenia. Schizophr Res 128: 171-172.

Responsible Party: Tony George, Professor, MD, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01465074     History of Changes
Other Study ID Numbers: NICPAS#024/2011
Study First Received: November 1, 2011
Last Updated: August 9, 2013
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
nicotine
memory
plasticity
TMS
Paired Associative Stimulation

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 September 30, 2014