Cigarette Smoking in Smokers With and Without Schizophrenia

Study Overview
=================
Brief Summary
-----------------
Higher rates and severity of tobacco dependence in people with schizophrenia, as compared with the general population, contribute to the lower life expectancy seen in this population. Dependent tobacco smoking is controlled by how different aspects of cigarette smoking are perceived. There is evidence suggesting that people with schizophrenia differ in how they perceive cigarette smoking, which, if confirmed, would have implications for tailoring treatment interventions for smoking cessation in schizophrenia.

Detailed Description
-----------------
The aim of the present study is to determine whether tobacco smoking in people with schizophrenia is governed by different aspects and effects of cigarette consumption. Smokers participating in this study either have no psychiatric diagnosis, or a diagnosis of schizophrenia or schizoaffective disorder. Over four study visits, participants will sample and compare different research cigarettes, complete questionnaires and concentration tasks, and smoke one type of research cigarette for eight hours while wearing a nicotine patch. By shaping our understanding of tobacco dependence in schizophrenia, the present project may redirect treatment development toward strategies tailored to the specific vulnerabilities of this population, which is among the most severely affected by its detrimental impact on health and life.

Official Title
-----------------
Cigarette Smoking in Smokers With and Without a Diagnosis of Schizophrenia

Conditions
-----------------
Tobacco Dependence, Schizophrenia

Intervention / Treatment
-----------------
* Combination Product: Sampling Research Cigarettes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Regular smoker of at least 10 cigarettes or cigarillos/day for at least 2 years For participants with schizophrenia: DSM-5 diagnosis of schizophrenia or schizoaffective disorder For participants with schizophrenia: Able to give informed consent For smokers with schizophrenia: No change in psychiatric medication or dosage in the last 4 weeks Exclusion Criteria: Uncontrolled hypertension (resting systolic BP above 150 or diastolic above 95 mm Hg) Cardiovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, severe arrhythmias, or EKG abnormalities Severe asthma Chronic obstructive pulmonary disease Neurological illness, such as stroke, seizure disorder, neurodegenerative disease, or organic brain syndrome Mental retardation Alcohol or substance use disorder except nicotine within the last year Use of benztropine (Cogentin), varenicline (Chantix), bupropion (Wellbutrin, Zyban), or any type of nicotine replacement Pregnant or lactating For healthy control smokers: DSM-5 diagnosis of depression, bipolar disorder, ADHD, autism spectrum disorder, anorexia, bulimia nervosa, or any schizophrenia-spectrum disorder For healthy control smokers: immediate family history of psychosis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will compare participants with and without a diagnosis of schizophrenia. Study procedures are identical for the two groups.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Smokers with schizophrenia<br>This is a diagnostic group, defined independently from this study. | Combination Product: Sampling Research Cigarettes<br>* Participants sample two research cigarettes, which differ in typical tobacco smoke constituents such as tar, nicotine, carbon monoxide, etc. In the Cigarette Discrimination Session, participants sample both types of cigarettes repeatedly, guess their identity (A or B) with regard to reference cigarettes, and rate their subjective effects. In the Ad Libitum Smoking Session, participants can smoke one of these cigarette types as much or as little as they like for eight hours.<br>|
| Other: Smokers without schizophrenia<br>This is a diagnostic group (i.e., no diagnosis of schizophrenia), defined independently from this study. | Combination Product: Sampling Research Cigarettes<br>* Participants sample two research cigarettes, which differ in typical tobacco smoke constituents such as tar, nicotine, carbon monoxide, etc. In the Cigarette Discrimination Session, participants sample both types of cigarettes repeatedly, guess their identity (A or B) with regard to reference cigarettes, and rate their subjective effects. In the Ad Libitum Smoking Session, participants can smoke one of these cigarette types as much or as little as they like for eight hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in exhaled carbon monoxide | The concentration (ppm) of carbon monoxide (CO) in breath is measured by exhalation into a CO breathalyzer at the beginning of the Ad Libitum Smoking Session (baseline), and at the end eight hours later. The change value is obtained by subtracting each participant's baseline value from the end-of-session value. | One day (in the Ad Libitum Smoking Session), over an 8-hour time frame. | 
| Cigarette Discrimination Accuracy | Participants sample 4 cigarettes of type A and 4 cigarettes of type B in a double-blind manner and indicate for each cigarette if they think it is of type A or B. Two reference trials with cigarette type unblinded will be performed before the first and fifth sample cigarette. For each sampled cigarette, the score is either 1 (correct) or 0 (incorrect). Discrimination accuracy is calculated by averaging the eight scores for each participant. | One day (in the Cigarette Discrimination Session), over a 6-hour time frame. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of research cigarettes smoked | In the Ad Libitum Smoking Session, participants can smoke as many research cigarettes as they wish. We quantify the number of cigarettes smoked in the first two hours and in the last two hours of the session and calculate the difference score by subtracting the number in the last two hours from that in the first two hours. | One day (in the Ad Libitum Smoking Session), over an 8-hour time frame. | 
| Difference in subjective state composite score | The difference in subjective state composite score is derived by transforming each subject's score on the Minnesota Nicotine Withdrawal Scale, the Affect-based Withdrawal Scale, the Questionnaire for Smoking Urges, and the modified Cigarette Evaluation Questionnaire into standard z-scores, calculating the difference between Research Cigarette A and B for each scale, and averaging the absolute values across scales. | One day (in the Cigarette Discrimination Session), over a 6-hour time frame. |