Nicotine Use Disorder
Conditions
Keywords
Nicotine Addiction, Quitting Smoking
Brief summary
The purpose of this research study is to better understand why people gain weight when they quit smoking by examining food intake and changes in brain activity in smokers when they are smoking as usual compared to when they have been deprived of cigarettes (i.e., have not smoked for 4 days) as compared to a non-smoker control group.
Detailed description
Tobacco use and obesity are the two leading causes of preventable deaths. Because these two behaviors share common brain reward mechanisms, reducing one behavior often leads to increases in the other behavior. Behavioral Economic and Incentive Salience models shed much light on this clinical problem. Smoking cessation produces reward dysregulation that can alter the motivational salience of other reinforcers, particularly food. After stopping smoking, smokers increase between-meal snacking, especially foods high in fat and sugar. Increases in caloric intake occur within days of quitting smoking, and are clinically significant. The investigators have also shown that smoking cessation produces working memory deficits and reduces activity in the brain's cognitive control circuits, making it even more difficult to exert self-control over temptations to eat highly rewarding foods. Thus, smokers have a double challenge: food becomes more salient and reinforcing at a time when their neurocognitive resources are compromised. Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. The proposed functional magnetic resonance imaging (fMRI) study breaks new ground by integrating concepts and tools from the fields of behavioral economics and cognitive neuroscience to accelerate the study of mechanisms underlying PCWG. The investigators will use a previously validated within-subject crossover neuroimaging study design to examine changes in working memory, food salience (cue-induced craving), and food reinforcement processes in the brain after 4 days of smoking cessation (vs. smoking as usual). A non-smoker control group will provide insight into baseline differences from smokers (abstinent and satiated). Caloric intake, the primary outcome, will be assessed using 24-hr. food recalls during each study period. The investigators will assess three parallel pathways including: working memory, food cue reactivity, and food reinforcement at the neural and behavioral levels. This study will provide new insights about how the brain can constrain or promote the ability of smokers to prevent post cessation weight gain (PCWG) and lead to new interventions that integrate neural and behavioral framework. Support for our predictions would inform testing of novel approaches to prevent PCWG, such as computerized neurocognitive exercise training to increase DLPFC activity and shift activity away from reward sensitive brain networks.
Interventions
OTHERPractice Quit Attempt
Smokers will be studied under 2 conditions: smoking as usual and during a 4 day practice quit attempt.
Sponsors
University of Pennsylvania
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Smoking participants will be studding under both smoking as usual and abstinent conditions (crossover) and non-smokers only under abstinence.
Intervention model description
This is a within-subject cross-over neuroimaging investigation of 3 potential neural mechanisms of increased caloric intake during initial smoking cessation. Eighty smokers will be scanned on 2 occasions: (1) after 4 days of monitored abstinence (biochemically verified), and (2) after 4 days of smoking as usual (order counterbalanced). In addition, 30 healthy non-smokers (matched for sex, age, and education) will complete one period of the study to serve as a baseline comparison group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Male and female participants who are between 18 and 45 years of age. Smoking group - 80 treatment-seeking smokers who self-report smoking at least 10 cigarettes (menthol and/or non-menthol) per day for at least the last 6 months. Smoking status will be confirmed by CO greater than or equal to 8 parts per million (ppm) at the Intake Visit. Non-smoking group - 30 individuals reporting fewer than 100 lifetime cigarettes and not even a puff of a cigarette for a minimum of 2 years. Smoking status of non-smokers will be confirmed by CO less than 5ppm. They will be matched to the smoker group on age, sex, and education. Plan to live in the area for the duration of the study (i.e. \ 8 weeks/2 months). Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form. Smokers who wish to make a permanent quit attempt in the next 1-2 months (treatment-seeking), because our prior work suggests that motivated subjects are more sensitive to medication effects on smoking behavior. Using a scale from 0 to 100 (100, being extremely interested), subjects must rate their interest in quitting smoking within the next 1-2 months greater than 50. Able to communicate fluently in English (i.e. speaking, writing, and reading).
Exclusion criteria
Subjects who present and/or self-report with the following criteria will not be eligible to participate in the study: Smoking Behavior 1. Regular use of nicotine-containing products other than cigarettes (e.g. chewing tobacco, snuff, snus, cigars, e-cigs, etc.). Participants agreeing to abstain from using nicotine- containing products other than cigarettes will be considered eligible. 2. Current enrollment or plans to enroll in another research and/or smoking cessation program over the duration of the study (i.e. \ 8 weeks/2 months). 3. Anticipated use (within the next \ 8 weeks/2 months) of any nicotine substitutes and/or smoking cessation treatments/medications unless provided through the study. 4. Provide a CO breath test reading less than 8 ppm at Intake Visit (smokers) or greater than 5ppm at intake visit (non-smokers). Alcohol and Drug 1. History of substance abuse (other than nicotine) in the past 12 months and/or currently receiving medical treatment for substance abuse. Counseling and support groups (e.g. Alcoholics Anonymous and Narcotics Anonymous) will not be considered medical treatment for the purposes of this protocol. 2. Current alcohol consumption that exceeds 25 standard drinks/week. 3. Breath alcohol reading (BrAC) greater than .000 at the Intake Visit. 4. A positive urine drug screen (UDS) for cocaine, opiates, amphetamines, methamphetamines, phencyclidine (PCP), ecstasy (MDMA), barbiturates, benzodiazepines, methadone, and/or oxycodone at the Intake Visit. Medical 1. Women who are pregnant, breast feeding, or planning a pregnancy over the duration of the study period. Women must agree to use an adequate form of contraception or abstain from sexual intercourse for the duration of the study. 2. Current treatment of cancer or diagnosed with cancer (except basal or squamous-cell carcinoma not treated with chemotherapy and/or radiation) in the past 6 months. 3. Poorly controlled, brittle, or pump-dependent Type I diabetes. 4. Current peptic ulcer bleeding. 5. Active hepatitis or poorly controlled kidney and/or liver disease. 6. Serious or unstable disease within the past 6 months. Notable diseases will be evaluated on a case-by-case basis by the Principal Investigator and/or the Study Physician. 7. Any impairment including, but not limited to, visual, physical, and/or neurological impairments preventing proper completion of the study procedures. Notable impairments will be evaluated on a case-by-case basis by the Principal Investigator and/or the Study Physician. 8. Applicable food allergies or disorders: * Galactosemia a * Notable milk allergy (lactose intolerant participants may proceed unless they experience severe symptoms) b * Notable soy allergy c * Peanut allergy d a,b,c Boost® Original Very Vanilla Nutritional Shake: Contains milk and soy ingredients. Suitable for Lactose Intolerance. 1. b,c,d M&M's® (Milk Chocolate): Contains milk and soy ingredients (MAY CONTAIN PEANUTS) Lay's® Classic Potato Chips (Gluten Free): Potatoes, vegetable oil, and salt Psychiatric 1. Current diagnosis of major depression. Subjects with a history of major depression, in remission for 6 months or longer (may be stable on antidepressant medications), are eligible. 2. Lifetime history of a suicide attempt. 3. Lifetime history of schizophrenia, psychosis, and/or bipolar disorder. 4. Current diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD). 5. Current diagnosis of bulimia, anorexia nervosa or binge eating. Medication Current use or recent discontinuation (within the last 14 days) of: 1. Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin SR, Chantix). 2. Benzodiazepines and/or Barbiturates. 3. Anti-psychotic medications. 4. Prescription stimulants (e.g., Provigil, Ritalin, Adderall). 5. Systemic steroids. 6. Medications for the use of addiction treatment. Current use of: 7. Nicotine replacement therapy (NRT). 8. Heart medications such as digoxin, quinidine, and nitroglycerin. Daily use of: 9. Opiate-containing medications for chronic pain. 10. Inhaled corticosteroids. Subjects will be instructed to refrain from using any study-prohibited drugs/medications (both recreational and prescription) throughout their participation in the study. After final eligibility is confirmed, subjects who report taking contraindicated medication(s) over the course of the study period may only remain eligible if the Study Physician and Principal Investigator determine that the contraindicated medication(s) do/did not significantly impact the study design, data quality, and/or subject safety and welfare. Subjects are permitted to take necessary prescription medications not included within the exclusion list during the study. General Exclusion 1. Past, current, anticipated, or pending enrollment in another research program over the study period that could potentially impact subject safety, study data, and/or the study design as determined by the Principal Investigator and/or Study Physician. 2. Participation in a dietary program within the past 30 days. 3. Any medical condition, illness, disorder, adverse event (AE), or concomitant medication that could compromise participant safety or significantly impact study performance as determined by the Principal Investigator and/or Study Physician. Subjects may be deemed ineligible for any of the aforementioned reasons at any point throughout the study, as well as during the initial telephone screen. 4. Significant non-compliance with protocol and/or study design as determined by the Principal Investigator and/or Study Physician. Subjects may be deemed ineligible at any point throughout the study. 5. Low or borderline intellectual functioning - determined by receiving a score of less than 85 on the Shipley Institute of Living Scale (SILS), which correlates with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test. fMRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abstinence Induced Change in Task BOLD Signal Change | BOLD fMRI is collected on days 4 and 32 of protocol | The primary outcome measure is change in BOLD signal for the Food Cue-Induced Craving primary regions of interest for the BOLD fMRI analysis are anterior cingulate gyrus (ACC), Insula, Ventral Striatum (VS), and orbital frontal cortex (OFC). For the Working Memory N-Back Task the primary regions of interest for the BOLD analysis will be dorsal lateral prefrontal cortex (DLPFC) and posterior cingulate gyrus (PCC). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Smoking Then Abstinent Group The Smoking then Abstinent Group group will be scanned on 2 occasions:(1) after 4 days of smoking as usual, and (2) after a 4-day monitored practice quit attempt (biochemically verified). | 25 |
| Abstinent Then Smoking Group The Abstinent then Smoking Group group will be scanned on 2 occasions: (1) after a 4-day monitored practice quit attempt (biochemically verified), and (2) after 4 days of smoking as usual. | 26 |
| Non-Smoking Comparison Group Healthy non-smokers will complete one period (comparable to abstinence arm) of the study to serve as a baseline comparison group. | 31 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Scan 1(Smoking, Abstinent or Non-smoker) | change in eligibility | 3 | 4 | 1 |
| Scan 1(Smoking, Abstinent or Non-smoker) | Lost to Follow-up | 4 | 3 | 2 |
| Scan 1(Smoking, Abstinent or Non-smoker) | Withdrawal by Subject | 1 | 1 | 1 |
| Washout Period (Smoking or Abstinent) | change in eligibility | 3 | 2 | 0 |
| Washout Period (Smoking or Abstinent) | Lost to Follow-up | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Smoking Then Abstinent Group | Abstinent Then Smoking Group | Non-Smoking Comparison Group | Total |
|---|---|---|---|---|
| Age, Continuous | 51.38 years STANDARD_DEVIATION 14.31 | 46.40 years STANDARD_DEVIATION 13.68 | 39.65 years STANDARD_DEVIATION 14.86 | 43.74 years STANDARD_DEVIATION 15.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 21 Participants | 29 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 16 Participants | 18 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 20 Participants | 42 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 11 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 31 | 0 / 28 | 0 / 31 |
| other Total, other adverse events | 3 / 51 | 0 / 31 | 2 / 28 | 1 / 31 |
| serious Total, serious adverse events | 0 / 51 | 0 / 31 | 0 / 28 | 0 / 31 |
Outcome results
Primary
Abstinence Induced Change in Task BOLD Signal Change
The primary outcome measure is change in BOLD signal for the Food Cue-Induced Craving primary regions of interest for the BOLD fMRI analysis are anterior cingulate gyrus (ACC), Insula, Ventral Striatum (VS), and orbital frontal cortex (OFC). For the Working Memory N-Back Task the primary regions of interest for the BOLD analysis will be dorsal lateral prefrontal cortex (DLPFC) and posterior cingulate gyrus (PCC).
Time frame: BOLD fMRI is collected on days 4 and 32 of protocol
Population: The smoking and abstinent fMRI session population is comprised of all smokers completing two fMRI sessions. The healthy comparison group is composed of all control group participants completing one fMRI scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left VS) | -0.057 percentage of signal change | Standard Deviation 0.359 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (posterior cingulate cortex) | -0.081 percentage of signal change | Standard Deviation 0.202 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (OFC) | 0.015 percentage of signal change | Standard Deviation 0.227 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right VS) | -0.050 percentage of signal change | Standard Deviation 0.33 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (ACC) | 0.000 percentage of signal change | Standard Deviation 0.25 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (right dorsal lateral prefrontal cortex) | 0.231 percentage of signal change | Standard Deviation 0.214 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right Insula) | 0.057 percentage of signal change | Standard Deviation 0.263 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left Insula) | 0.051 percentage of signal change | Standard Deviation 0.252 |
| Smoking fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (left dorsal lateral prefrontal cortex) | 0.211 percentage of signal change | Standard Deviation 0.202 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right VS) | 0.053 percentage of signal change | Standard Deviation 0.625 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (ACC) | -0.014 percentage of signal change | Standard Deviation 0.233 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left Insula) | -0.011 percentage of signal change | Standard Deviation 0.254 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right Insula) | -0.013 percentage of signal change | Standard Deviation 0.266 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left VS) | 0.062 percentage of signal change | Standard Deviation 0.559 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (OFC) | 0.034 percentage of signal change | Standard Deviation 0.338 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (left dorsal lateral prefrontal cortex) | 0.180 percentage of signal change | Standard Deviation 0.237 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (right dorsal lateral prefrontal cortex) | 0.196 percentage of signal change | Standard Deviation 0.239 |
| Abstinent fMRI Session | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (posterior cingulate cortex) | -0.096 percentage of signal change | Standard Deviation 0.215 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right Insula) | 0.057 percentage of signal change | Standard Deviation 0.246 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (ACC) | 0.027 percentage of signal change | Standard Deviation 0.215 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (left dorsal lateral prefrontal cortex) | 0.211 percentage of signal change | Standard Deviation 0.378 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left Insula) | 0.055 percentage of signal change | Standard Deviation 0.247 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (posterior cingulate cortex) | -0.142 percentage of signal change | Standard Deviation 0.273 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Right VS) | 0.014 percentage of signal change | Standard Deviation 0.368 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (Left VS) | 0.010 percentage of signal change | Standard Deviation 0.497 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | N-Back Task (right dorsal lateral prefrontal cortex) | 0.243 percentage of signal change | Standard Deviation 0.406 |
| Non-Smoking Comparison Group | Abstinence Induced Change in Task BOLD Signal Change | Food Induced Craving (OFC) | 0.104 percentage of signal change | Standard Deviation 0.341 |