Effects of Acute Nicotine Treatment on Neuroplasticity and Memory in Patients With Schizophrenia

NCT01465074 | Terminated

• 1 other identifier: NICPAS#024/2011
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia

Keywords

nicotine; memory; plasticity; TMS; Paired Associative Stimulation

Outcome Measures

Primary Outcomes (1)

• Change in prefrontocortical neuroplasticity

  Change in cortical evoked activity (using EEG) from baseline to the different time points following paired associative stimulation.

  0, 15, 30, 60, 120 min, 7 days post treatment

Secondary Outcomes (1)

• Change in working memory

  baseline, 30 and 120 min and 7 days post treatment

Study Arms (2)

Nicotine gum (4 mg)

ACTIVE COMPARATOR

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

Regular Mint Gum

PLACEBO COMPARATOR

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

Interventions

Nicotine polacrilex DRUG

4 mg

Also known as: Nicorette, Extreme Chill

Nicotine gum (4 mg)

Regular chewing gum; Dentyne Ice, Wrigely´s Mint Gum DRUG

30 min chewing, one dose

Regular Mint Gum

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (10)

• Weinberger DR, Berman KF, Zec RF. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry. 1986 Feb;43(2):114-24. doi: 10.1001/archpsyc.1986.01800020020004.

  PMID: 3947207 BACKGROUND

• Green MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry. 2006;67 Suppl 9:3-8; discussion 36-42.

  PMID: 16965182 BACKGROUND

• Moss TG, Sacco KA, Allen TM, Weinberger AH, Vessicchio JC, George TP. Prefrontal cognitive dysfunction is associated with tobacco dependence treatment failure in smokers with schizophrenia. Drug Alcohol Depend. 2009 Sep 1;104(1-2):94-9. doi: 10.1016/j.drugalcdep.2009.04.005. Epub 2009 May 17.

  PMID: 19447570 BACKGROUND

• Wing VC, Sacco KA, George TP. Spatial working memory impairments induced by cigarette smoking abstinence are correlated with plasma nicotine levels in schizophrenia. Schizophr Res. 2011 May;128(1-3):171-2. doi: 10.1016/j.schres.2010.10.011. Epub 2010 Nov 13. No abstract available.

  PMID: 21075601 BACKGROUND

• Lewis DA, Gonzalez-Burgos G. Neuroplasticity of neocortical circuits in schizophrenia. Neuropsychopharmacology. 2008 Jan;33(1):141-65. doi: 10.1038/sj.npp.1301563. Epub 2007 Sep 5.

  PMID: 17805309 BACKGROUND

• Daskalakis ZJ, Christensen BK, Fitzgerald PB, Chen R. Dysfunctional neural plasticity in patients with schizophrenia. Arch Gen Psychiatry. 2008 Apr;65(4):378-85. doi: 10.1001/archpsyc.65.4.378.

  PMID: 18391126 BACKGROUND

• Thirugnanasambandam N, Grundey J, Adam K, Drees A, Skwirba AC, Lang N, Paulus W, Nitsche MA. Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans. Neuropsychopharmacology. 2011 Mar;36(4):879-86. doi: 10.1038/npp.2010.227. Epub 2010 Dec 15.

  PMID: 21160466 BACKGROUND

• Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, Daskalakis ZJ. Reliability of long-interval cortical inhibition in healthy human subjects: a TMS-EEG study. J Neurophysiol. 2010 Sep;104(3):1339-46. doi: 10.1152/jn.00279.2010. Epub 2010 Jun 23.

  PMID: 20573972 BACKGROUND

• Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000 Mar;123 Pt 3:572-84. doi: 10.1093/brain/123.3.572.

  PMID: 10686179 BACKGROUND

• Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, Daskalakis ZJ. Evidence for gamma inhibition deficits in the dorsolateral prefrontal cortex of patients with schizophrenia. Brain. 2010 May;133(Pt 5):1505-14. doi: 10.1093/brain/awq046. Epub 2010 Mar 28.

  PMID: 20350936 BACKGROUND

Related Links

• Information about research at the Centre for Addiction and Mental Health

MeSH Terms

Conditions

Schizophrenia

Interventions

Tobacco Use Cessation Devices; Nicotine Chewing Gum

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 4, 2011
• Study Start: November 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: August 13, 2013

Record last verified: 2013-08

Locations

CA (1)