Official Title: “Influence of Nicotine on Cognitive Function in Schizophrenic Patients With and Without Comorbid Drug Dependence”

We aim to study schizophrenia patients with comorbid drug dependence, comparing them to non-drug-dependent individuals with schizophrenia and to healthy control subjects. We expect that patients with comorbid drug dependence will have the worst performance in measures of eyetracking, attention and memory as compared to the other two groups. The second goal of this study is to understand how nicotine may improve some of these neurocognitive and neurophysiological deficits with dual diagnosis patients.

Study Type: Interventional

Study Design: Other, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment

Study Primary Completion Date: November 2009

We propose to assess the potential dose-related benefit of nicotine on eye tracking, attention and memory processes in schizophrenic patients with and without comorbid drug dependence. This is a collaborative outpatient study between NIDA and the Schizophrenia and Related Disorders (SRD) unit at the MPRC.

First, we will conduct a separate Pilot Study, recruiting 10 participants with schizophrenia to determine the parameters of the behavioral tasks to ensure approximately 75% accuracy at baseline.

Next, we will conduct the Main Study in which we will compare the dual-diagnosis patient group to non-drug-dependent individuals with schizophrenia and to healthy control subjects.

We expect that patients with comorbid drug dependence will have the worst performance in anticipatory learning of eyetracking, attention, and memory as compared to the other two groups, and that patients without illicit drug dependence will be intermediate between the above two groups. The second goal of this study is to determine if nicotine will dose-dependently improve these neurophysiological and cognitive processes in individuals with comorbid schizophrenia and substance dependence. We hypothesize that the transient beneficial effect of nicotine on individuals with schizophrenia only and in healthy control subjects will be significant but intermediate in the extent of improvement as compared to the comorbid group.

This study will be a double-blind, placebo controlled trial of nicotine or placebo nasal sprays. The study will require 4 sessions. The first will be an introductory session of 2-3 hours during which the participant will sign the consent form, provide a breath sample to measure expired air carbon monoxide, and the participant will be familiarized with the tasks and questionnaires. The highest dose of nicotine nasal spray (2.0 mg) will be administered to assess tolerability and to familiarize participants with the effect of the spray.

The 3 experimental sessions will be comprised of cognitive testing and vital sign monitoring.

One dose of nicotine (0, 1 or 2 mg) will be administered twice during each experimental session. The eyetracking battery and memory/attention battery each last approximately 35 minutes. Nicotine will be administered 5 minutes prior to each test battery, with 90 minutes between drug administration which is sufficient time for subjective or cognitive effects of the previous dose to dissipate (Myers et al., 2004; Perkins et al., 1994). Thus, participants will receive one dose level of nicotine, administered twice, in each of the 3 experimental sessions. These sessions will be counterbalanced, last about 3 hours, and will be scheduled at least 12 hours apart.

The scientific goals of this study are to (1) determine if, in schizophrenic smokers, comorbid drug dependence predicts differences in cognitive processes that are impaired in schizophrenia; (2) determine if nicotine will dose-dependently attenuate these cognitive deficits for both groups of schizophrenic smokers; and enhance memory, attention and eyetracking performance in cognitively normal individuals. Data will be analyzed using multivariate repeated measures ANOVA in SPSS followed by specific post hoc tests.

Intervention(s) in this Clinical Trial

• Drug: 2 mg nicotine nasal spray (Nicotrol NS)
  • One spray of the active Nicotrol NS (Pharmacia Corp., Peapack NJ) delivers 0.5 mg nicotine, so 4 sprays are needed for the 2 mg dose. The amount of nicotine in the 2 mg dose is equivalent the amount of nicotine in 1-2 cigarettes. A subject would receive this dose unblinded on the Consent/Training Day and twice on one of the three blinded experimental days, with dosing before eye-tracking and computer task battery sessions.
• Drug: 1 mg nicotine nasal spray (Nicotrol NS)
  • One spray of the active Nicotrol NS (Pharmacia Corp., Peapack NJ) delivers 0.5 mg nicotine, so 2 sprays are needed for the 1 mg dose. To ensure blinding of subjects and investigator, the pharmacy will provide 2 bottles for each dose, such that the 1 mg dose will consist of 2 sprays of active Nicotrol and 2 of placebo. The amount of nicotine in the 1 mg dose is equivalent the amount of nicotine in 1 cigarette. A subject would receive this dose twice on one of the three blinded experimental days, with dosing before eye-tracking and computer task battery sessions.
• Drug: 0 mg nicotine nasal spray (Placebo)
  • The NIDA Pharmacy staff will prepare the placebo spray by adding 5 microliters of 3% capsaicin solution to 20 milliliters of sterile saline, producing a capsaicin concentration of 0.00075%. This placebo spray produces a nasal irritation very similar in magnitude and duration (less than 3 minutes) to that of the nicotine nasal spray (Nicotrol NS), thus providing an effective placebo. To ensure blinding of subjects and investigator, the pharmacy will provide 2 bottles for each dose, such that the placebo dose will consist of 4 sprays of the placebo Nicotrol.

Arms, Groups and Cohorts in this Clinical Trial

• Other: 1
  • Smokers who are patients with a DSM-IV diagnosis of schizophrenia (Single Dx Group)
• Other: 2
  • Smokers who are patients with dual DSM-IV diagnoses of schizophrenia and heroin and/or cocaine dependence or abuse (Dual Dx Group)
• Other: 3
  • Smokers who are healthy individuals with no family history of psychotic illness (Control group)

Primary Measures

• Dependent variables: For working memory, delayed recognition and attention tasks: percent of correct responses and response time; For eye-tracking tasks: initiation latency, initiation acceleration, and maintenance pursuit gain.
  • Time Frame: The 30 minutes after the nicotine administration in which the subjects complete either the eye-tracking or the computer task battery.
    Safety Issue?: No

Inclusion Criteria:

All participants must meet the following criteria:

• Age 18 - 55
• Smoker 10 for at least the past year

Experimental groups 1 and 2, additional criteria:

• DSM-IV diagnosis of schizophrenia or schizoaffective disorder

Experimental group 2, additional criteria:

• DSM-IV diagnosis of heroin and/or cocaine abuse or dependence

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Maryland

Overall Clinical Trial Officials and Contacts

Carol S Myers, PhD Principal Investigator National Institute on Drug Abuse (NIDA)  

Overall Contact: Katherine S Wright, BA 410-402-6415 KWright@mprc.umaryland.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00686153

Study ID Number: H-27070

ClinicalTrials.gov Identifier: NCT00686153

Health Authority: United States: Institutional Review Board