Racial Differences in Circadian and Sleep Mechanisms for Nicotine Dependence, Craving, and Withdrawal

Study Overview
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Brief Summary
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The number one preventable cause of death in the world is tobacco use. Cigarette smoking in particular, costs an estimated $300 billion due to expenses related to medical care and lost productivity. Despite similar smoking prevalence rates, blacks suffer disproportionately from smoking-related harms compared to whites.Sleep disparities such as shortened sleep duration, shorter circadian periodicity, earlier chronotype, and increased variability of sleep timing have been reported more frequently in blacks compared to whites. Given that poor sleep quality predicts relapse from smoking cessation programs, particularly among socioeconomically disadvantaged adults, sleep deficiencies and irregular timing of sleep may impact smoking craving and withdrawal symptoms over the course of the 24-hour day. Surprisingly, few studies have examined these temporal patterns of smoking and craving, and none with regard to sleep disruption, chronotype or racial disparities. A better understanding of these factors may explain heterogeneity within the smoking population, especially in minorities. Thus, the purpose of this proposal is to test the central hypothesis that the impact of chronotype and impaired sleep on cigarette usage as well as smoking dependence, urge/craving, and withdrawal depends on race.

Detailed Description
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Three specific aims will determine: contributions of sleep timing and sleep quality and quantity to racial disparities in smoking status (Aim 1), objective sleep characteristics and smoking behavior among blacks and whites who smoke cigarettes (Aim 2), and whether sleep restriction modifies craving and withdrawal in racially diverse smokers (Aim 3). Specifically, we will utilize self-report questionnaires, objective measures of sleep quality and timing (actigraphy) and circadian phase (dim light melatonin onset), as well as ecological momentary assessment of cigarette use, smoking urges, cravings, and withdrawal symptoms to identify circadian and sleep characteristics that are most strongly associated with smoking status, heaviness of smoking and dependence among blacks and whites. Finally, we will test whether acute sleep restriction (4 hours of time-in-bed) versus sleep extension (10 hours of time-in-bed) modifies craving and withdrawal symptoms following cessation in black and white smokers. If successful, the results of this study will result in identification of circadian dysfunction and insufficient sleep as mechanisms that underlie the association between sleep and cigarette smoking behaviors and dependence in diverse populations. Moreover, these findings are likely to inform clinicians of the importance of sleep and sleep timing on cigarette smoking behaviors and dependence that will help in the development of novel interventions to reduce morbidity and mortality caused by tobacco use.

Official Title
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Racial Differences in Circadian and Sleep Mechanisms for Nicotine Dependence, Craving, and Withdrawal

Conditions
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Smoking, Sleep Disturbance, Nicotine Dependence

Intervention / Treatment
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* Behavioral: Sleep restriction condition
* Behavioral: Sleep extension condition


Participation Criteria
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Eligibility Criteria
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Sub-Study 1 Inclusion Criteria: 18 years or older Able to read and speak English Non-Hispanic African American (Black) or non-Hispanic white race Daily smoker (5 or more cigarettes a day for the past one year and having smoked more than 100 cigarettes in lifetime) or non-smoker (smoked fewer than 100 cigarettes in a lifetime and no smoking-not even a puff- in the last year) Currently residing in Alabama Exclusion Criteria: Non-English speaking Lives in restricted environment that does not allow smoking Pregnant or lactating Daily or exclusive use of other tobacco products (e.g., cigars, e-cigarettes) if a smoker; if non-smoker, any other tobacco product use is exclusionary Currently receiving smoking cessation treatment or using electronic cigarettes or other tobacco to try and quit smoking cigarettes Participants would work outside normal 7 a.m. to 6 p.m. hours Former smokers Sub-study 2 Inclusion Criteria: 18 years or older Able to read and speak English Non-Hispanic African American (Black) or non-Hispanic white race Daily smoker defined as smoking 5 or more cigarettes a day for the past one year and having smoked more than 100 cigarettes in lifetime, as well as by an expired Carbon Monoxide (CO )cut-off of Carbon Monoxide (CO)>10ppm and positive cotinine test to ensure daily smoking OR non-smoker defined as smoking fewer than 100 cigarettes in a lifetime and no smoking-not even a puff- in the last year, as well as by an expired Carbon monoxide (CO) cut-off of Carbon Monoxide (CO)<3 ppm and negative cotinine test. Currently residing in Alabama Exclusion Criteria: Non-English speaking Lives in restricted environment that does not allow smoking Pregnant or lactating Testing positive on urine drug screen test at baseline - any drugs other than Tetrahydrocannabinol (THC) not allowed Daily or exclusive use of other tobacco products (e.g., cigars, e-cigarettes) if a smoker; if non-smoker, any other tobacco product use is exclusionary Currently receiving smoking cessation treatment or using electronic cigarettes or other tobacco to try and quit smoking cigarettes Participants would work outside normal 7 a.m. to 6 p.m. hours Former smokers History of a medical condition (e.g., bipolar disorder, migraine, or seizure disorder) that might be exacerbated by sleep deprivation as a result of Study 3 History of a serious lung/breathing disease that prevents one from walking or holding their breath for 10 seconds (in order to complete Carbon Monoxide breath test) Cognitive impairment such that participant is unable to provide informed consent Acutely suicidal, manic, acutely intoxicated, or otherwise not stable enough to provide informed consent Living outside of the Birmingham metro area (> 20 miles away from University of Alabama at Birmingham Main Campus) Sub-study 3 Inclusion Criteria: 18 years or older Able to read and speak English Non-Hispanic African American (Black) or non-Hispanic white race Daily smoker defined as smoking 5 or more cigarettes a day for the past one year and having smoked more than 100 cigarettes in lifetime, as well as by an expired Carbon Monoxide (CO) cut-off of Carbon Monoxide (CO)>10ppm and positive cotinine test to ensure daily smoking Currently residing in Alabama Exclusion Criteria: Non-English speaking Lives in restricted environment that does not allow smoking Pregnant or lactating Daily or exclusive use of other tobacco products (e.g., cigars, e-cigarettes) if a smoker; if non-smoker, any other tobacco product use is exclusionary Currently receiving smoking cessation treatment or using electronic cigarettes or other tobacco to try and quit smoking cigarettes Participants would work outside normal 7 a.m. to 6 p.m. hours Former smokers History of a medical condition (e.g., bipolar disorder, migraine, or seizure disorder) that might be exacerbated by sleep deprivation as a result of Study 3 Currently taking any psychiatric medications, pain medications (i.e., opioids), or sleep medications (e.g., Ambien, trazodone, melatonin pills, Cannabidiol (CBD) products) History of a serious lung/breathing disease that prevents one from walking or holding their breath for 10 seconds Testing positive on urine drug screen test at baseline - any drugs other than Tetrahydrocannabinol (THC) not allowed Has an apnea-hypopnea index (AHI) score of > 15 on home sleep testing that was conducted during sub-study 2 Uses Continuous positive airway pressure (CPAP) machine to sleep at night Cognitive impairment such that participant is unable to provide informed consent Acutely suicidal, manic, acutely intoxicated, or otherwise not stable enough to provide informed consent Living outside of the Birmingham metro area (> 20 miles away from University of Alabama at Birmingham Main Campus)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep Restriction<br>4 hours time in bed (1 am to 5 am) | Behavioral: Sleep restriction condition<br>* On day 1, participants will complete study assessments and will be fitted with an Actiwatch and instructed to continue a fixed time in bed (8 hours duration with no more than 20 min deviation) centered on habitual sleep (e.g., 11:00 p.m. to 7:00 a.m.). Naps will not be allowed. Following the one-week baseline sleep stabilization, participants will engage in the sleep restriction condition (4 hours, TIB [Time in Bed]; 1:00 a.m. to 5:00 a.m.). On the day of each sleep study, participants will be admitted to University of Alabama Birmingham (UAB) Highlands Hospital sleep unit at 7:00 p.m. and do an initial CO breathe test and fill out study questionnaires and a timeline follow-back procedure Participants will monitored for smoking withdrawal. Every 2 hours, participants to fill out various questionnaires. Participants will repeat the same conditions as the first night. After a two-week washout, participants will be crossed over to the alternate sleep extension/restriction condition.<br>|
| Experimental: Sleep Extension<br>10 hours time in bed (10 pm to 8 am) | Behavioral: Sleep extension condition<br>* sleep extension On day 1, participants will complete study assessments and will be fitted with an Actiwatch and instructed to continue a fixed time in bed (8 hours duration with no more than 20 min deviation) centered on habitual sleep (e.g., 11:00 p.m. to 7:00 a.m.). Naps will not be allowed. Following the one-week baseline sleep stabilization, participants will engage in the sleep extension condition (10 hours, (TIB); 10:00 p.m. to 8:00 a.m.). On the day of each sleep study, participants will be admitted to University of Alabama Birmingham Highlands Hospital sleep unit at 7:00 p.m. and do an initial CO breathe test and fill out study questionnaires and a timeline follow-back procedure Participants will monitored for smoking withdrawal. Every 2 hours, participants to fill out various questionnaires. Participants will repeat the same conditions as the first night. After a two-week washout, participants will be crossed over to the alternate sleep extension/restriction condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Hygiene Index | A 13-item scale that assesses behaviors, such as variability in wake-time, timing of physical activity, and substance use, that comprise sleep hygiene 0: Never (Best) Rarely Sometimes Frequent Always (Worst) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index | A 7-item self-report measure that assesses global sleep quality over the past month. Additionally, sub-scales that include duration of sleep, sleep disturbance, sleep latency, daytime dysfunction, sleep efficiency, and dependence on hypnotic medication may be calculated from individual items Not during the past month (0; very good) Less than once a week once or twice a week Three or more times a week (3; very bad) | 6 months | 
| Munich Chronotype Questionnaire | Questionnaire that determines chronotype from midsleep time calculated from sleep onset and offset on both free days and work days. Chronotype will be determined from the mid-sleep time on days off . Specifically, Mid-sleep time is equal to Sleep onset + Sleep duration/2. For those who sleep longer on days off than on workdays, we will correct for weekend recovery sleep by subtracting 'sleep debt' accumulated, which is estimated by the following equation: Sleep duration on free days - Sleep duration (average) for the week/2. Chronotype will be categorized by either the median (two categories) or quartiles (to examine more extreme chronotypes). | 6 months | 
| Fagerström Test for Nicotine Dependence | A 6-item self-report measure of nicotine dependence derived from the Fagerström Tolerance Questionnaire 1-2: low dependence 3-4: low to mod dependence 5-7: moderate dependence 8+: high dependence | 6 months | 
| Snoring history, Tired during the day, Observed stop breathing while sleep, High blood pressure, BMI more than 35 kg/m2, Age more than 50 years, Neck circumference more than 40 cm and male Gender (STOP-BANG) Questionnaire | A 8-item self-report questionnaire that assesses the primary risk factors for obstructive sleep apnea to create a total score that ranges from 0 to 8 | 6 months | 
| Insomnia Severity Index | A 7-item self-report questionnaire that assesses the severity of core symptoms of insomnia over the previous 2 weeks | 6 months | 
| Dysfunctional Beliefs and Attitudes About Sleep (DBAS) | A 16-item questionnaire that assesses beliefs about sleep and the consequences of poor sleep | 6 months | 
| Epworth Sleepiness Scale (ESS) | A 8-item questionnaire that asks individuals to rate their chances of dozing off on a scale of 0 (never) to 3 (high) in eight different situations. The scores are summed to create a total score with higher values indicating higher chances of dozing off | 6 months | 
| Everyday Discrimination Scale (EDS) | This 9-item assessment queries about experiences of discrimination such as being treated less respectfully or people thinking that you are dishonest. Responses range from almost every day to never | 6 months | 
| Perceived Stress Scale - 10 Item (PSS-10) | Self-report questionnaire that assesses a person's perceived stress with a 5-point Likert scale ranging from Never to Very Often | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Race, smoking, sleep deficiencies, socioeconomic disadvantage