Schizophrenia, Tobacco Dependence
Conditions
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.
Interventions
COMBINATION_PRODUCTSampling Research Cigarettes
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.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants compare different research cigarettes. Neither the participant nor the investigators know which cigarette is of which type.
Intervention model description
We will compare participants with and without a diagnosis of schizophrenia. Study procedures are identical for the two groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| End-of-session Carbon Monoxide | One day (in the Ad Libitum Smoking Session), over an 8-hour time frame. | The concentration (ppm) of carbon monoxide (CO) in breath is measured by exhalation into a CO breathalyzer at the end of the 8-hour Ad Libitum Smoking Session. Only very-low-nicotine-content (virtually nicotine-free) cigarettes were consumed in this session. |
| Cigarette Discrimination Accuracy | One day (in the Cigarette Discrimination Session), over a 6-hour time frame. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Research Cigarettes Smoked | One day (in the Ad Libitum Smoking Session), over an 8-hour time frame. | In the Ad Libitum Smoking Session, participants can smoke as many research cigarettes (all very-low-nicotine-content) as they wish. The propensity to maintain smoking despite the absence of nicotine was quantified by subtracting the number of cigarettes smoked in the last two hours from that in the first two hours of the session. Smaller difference values indicate that smoking was upheld by very-low-nicotine-content cigarettes. |
| Difference in Subjective State Composite Score | One day (in the Cigarette Discrimination Session), over a 6-hour time frame. | The measure is derived by transforming scores on the Minnesota Nicotine Withdrawal Scale (where higher values signify more withdrawal), the Affect-based Withdrawal Scale (higher values signify a worse emotional state), Questionnaire for Smoking Urges (higher values indicate more craving), and modified Cigarette Evaluation Questionnaire (mCEQ, higher values indicate greater subjective effects of smoking on mood, hunger, physiology) into standard z-scores, thus giving each scale a mean of 0 and standard deviation of 1. Withdrawal and craving scores were re-poled (inversing the sign), and scales were averaged for each subject. The resulting composite quantified the subjective state response to cigarette smoking, larger values indicating less withdrawal, less craving, and larger effects on the mCEQ. The difference therein between the research cigarettes containing nicotine and those containing almost no nicotine quantified the subjective state response to nicotine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Smokers With Schizophrenia This is a diagnostic group, defined independently from this study.
Sampling Research Cigarettes: 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. | 18 |
| Smokers Without Schizophrenia This is a diagnostic group (i.e., no diagnosis of schizophrenia), defined independently from this study.
Sampling Research Cigarettes: 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. | 13 |
| Total | 31 |
Baseline characteristics
| Characteristic | Smokers With Schizophrenia | Smokers Without Schizophrenia | Total |
|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 11.9 | 48.3 years STANDARD_DEVIATION 7.5 | 43.7 years STANDARD_DEVIATION 11.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 2 Participants | 8 Participants |
| Region of Enrollment United States | 18 participants | 13 participants | 31 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 13 |
| other Total, other adverse events | 0 / 18 | 0 / 13 |
| serious Total, serious adverse events | 0 / 18 | 0 / 13 |
Outcome results
Primary
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.
Time frame: One day (in the Cigarette Discrimination Session), over a 6-hour time frame.
Population: One smoker with schizophrenia did not complete the study session in which this measurement was obtained, but completed the rest of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers With Schizophrenia | Cigarette Discrimination Accuracy | 65.6 percentage of choices that were correct | Standard Deviation 31.8 |
| Smokers Without Schizophrenia | Cigarette Discrimination Accuracy | 81.9 percentage of choices that were correct | Standard Deviation 11 |
Primary
End-of-session Carbon Monoxide
The concentration (ppm) of carbon monoxide (CO) in breath is measured by exhalation into a CO breathalyzer at the end of the 8-hour Ad Libitum Smoking Session. Only very-low-nicotine-content (virtually nicotine-free) cigarettes were consumed in this session.
Time frame: One day (in the Ad Libitum Smoking Session), over an 8-hour time frame.
Population: One smoker with schizophrenia and one smoker without schizophrenia did not complete the study session in which this measurement was obtained but completed all other study sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers With Schizophrenia | End-of-session Carbon Monoxide | 62.7 parts per million (ppm) | Standard Deviation 41.7 |
| Smokers Without Schizophrenia | End-of-session Carbon Monoxide | 43.0 parts per million (ppm) | Standard Deviation 23.3 |
Secondary
Change in the Number of Research Cigarettes Smoked
In the Ad Libitum Smoking Session, participants can smoke as many research cigarettes (all very-low-nicotine-content) as they wish. The propensity to maintain smoking despite the absence of nicotine was quantified by subtracting the number of cigarettes smoked in the last two hours from that in the first two hours of the session. Smaller difference values indicate that smoking was upheld by very-low-nicotine-content cigarettes.
Time frame: One day (in the Ad Libitum Smoking Session), over an 8-hour time frame.
Population: One smoker with schizophrenia and one smoker without schizophrenia did not complete the study session in which this measurement was obtained but completed the rest of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers With Schizophrenia | Change in the Number of Research Cigarettes Smoked | 1.75 difference in cigarettes smoked | Standard Deviation 4.3 |
| Smokers Without Schizophrenia | Change in the Number of Research Cigarettes Smoked | 1.50 difference in cigarettes smoked | Standard Deviation 0.93 |
Secondary
Difference in Subjective State Composite Score
The measure is derived by transforming scores on the Minnesota Nicotine Withdrawal Scale (where higher values signify more withdrawal), the Affect-based Withdrawal Scale (higher values signify a worse emotional state), Questionnaire for Smoking Urges (higher values indicate more craving), and modified Cigarette Evaluation Questionnaire (mCEQ, higher values indicate greater subjective effects of smoking on mood, hunger, physiology) into standard z-scores, thus giving each scale a mean of 0 and standard deviation of 1. Withdrawal and craving scores were re-poled (inversing the sign), and scales were averaged for each subject. The resulting composite quantified the subjective state response to cigarette smoking, larger values indicating less withdrawal, less craving, and larger effects on the mCEQ. The difference therein between the research cigarettes containing nicotine and those containing almost no nicotine quantified the subjective state response to nicotine.
Time frame: One day (in the Cigarette Discrimination Session), over a 6-hour time frame.
Population: One smoker with schizophrenia and one smoker without schizophrenia did not complete the study session in which this measurement was obtained. One additional smoker with schizophrenia did not complete the subjective state measurements but completed all other aspects of the session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers With Schizophrenia | Difference in Subjective State Composite Score | 0.13 difference in z-score | Standard Deviation 0.26 |
| Smokers Without Schizophrenia | Difference in Subjective State Composite Score | 0.039 difference in z-score | Standard Deviation 0.15 |