Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity
United States159 participantsStarted 2013-11-06
Plain-language summary
Background:
\- Smoking is a difficult habit to quit, and some people find it more difficult to quit than others do. Nicotine is the substance in cigarettes that makes smoking so addictive. Nicotine changes some patterns of brain activity, and smokers have differences in brain activity when compared to non-smokers. Some genes make it more likely that a person will become addicted to smoking. Researchers want to study how nicotine interacts with genes and brain activity. This may help develop better treatments to help people quit smoking.
Objectives:
\- To develop a test of nicotine dependence, using brain activity and genetic analysis, which may be useful in predicting success in smoking cessation and in the development of new smoking cessation treatment targets.
Eligibility:
* Main group: Current smokers between 18 and 55 years of age who are seeking treatment to quit.
* Comparison group: Current smokers between 18 and 55 years of age who are not seeking to quit.
* Comparison group: Healthy former smokers between 18 and 55 years of age.
* Comparison group: Healthy nonsmoking volunteers between 18 and 55 years of age.
Design:
* Participants will be screened with a physical exam and medical history. Blood samples will be collected.
* The three comparison groups will have one magnetic resonance imaging (MRI) scan session. They will have tests of thinking, concentration, and memory both inside the scanner, and while sitting in front of a computer.
* Current smokers who are trying to quit must be willing to undergo a course of nicotine treatment that includes weekly counseling (for 12 weeks) and e-cigarettes. Participants will attempt smoking abstinence and will have a total of 6 MRI scanning sessions. They will do thinking, concentration, and memory tasks inside and outside of the scanner.
* For smokers, the first scanning session will take place before they attempt to quit. This will be a baseline scan. The second scanning session will take place 48 hours after having their last real cigarette. After this scan, they will use electronic cigarettes to help quit their habit.
* After using e-cigarettes for two weeks, smokers will have a third scan session.. They will then gradually taper their use of the electronic cigarettes over the course of three weeks, at which point they will be nicotine abstinent.
* After about 5 weeks of abstinence, they will have the fourth scan. The fifth scan will be approximately 6 months after start of the study, and the final scan will take place at about 1 year from the study start.
* Smokers will continue to receive support on quitting smoking until the study ends at about 1 year.
Who can participate
Age range
18 Years – 60 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Be between the ages of 18-60. Assessment tool(s): Edinburgh Handedness Inventory. Although left-handed individuals will not be excluded, we will track handedness. Justification: Some of the neural processes assessed in this protocol may be lateralized in the brain. In order to assess potential variance, participants handedness will be documented.
. Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a medical history and physical examination with a qualified IRP clinician.
Exclusion criteria
. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to abstain from caffeine 24hrs before each session. Justification: Alcohol and caffeine modulate neural functioning in a way that would complicate data interpretation. Assessment tool(s): Self-report and breathalyzer.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This study tracked smoking status at 4 weeks, 3, 6, and 12 months — does the follow-up data from this completed trial show any patterns about which types of smokers were more or less likely to quit, and could that be relevant to my own situation?
2The trial involved brain imaging while participants were both on and off nicotine — what does that kind of research typically tell us about how nicotine affects brain activity, and how might that knowledge shape my treatment options?
3Since this study collected genetic and epigenetic data alongside brain scans, are there any findings from this type of research that could help explain why some people find nicotine so much harder to quit than others?
4The study measured craving, withdrawal symptoms, and mood during nicotine on and off conditions — based on what research like this has found, how should I expect those symptoms to affect my own quit attempt, and what support would you recommend?
5This trial is now completed and was more of an observational and imaging study than a treatment trial — are there any active treatment trials for nicotine dependence that you'd suggest I look into based on what studies like this one have learned?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups
Timeframe: each scan visit
2
Genetic and epigenetic data
Timeframe: each scan visit
3
Resting state MRI at follow-up
Timeframe: each scan visit
4
Behavioral performance on each task
Timeframe: each scan visit
5
Self-reported craving, withdrawal symptoms & mood/affect
. For the treatment and non-treatment seeking groups, must have a urine cotinine level corresponding to smoker/nicotine user status for the specific test being used (typically corresponding to a urine cotinine above about 200 ng/ml) and have been smoking or vaping consistently for at least the past year (excluding quit attempts). Based on the correlation between self-reported cpd/FTND and urine cotinine levels \[85a, 85b\], a single inclusion criterion will be easier to manage and provide adequate characterization of nicotine dependent participants. Urine cotinine level provides a biomarker that does not rely on self-report/memory. Quit attempts will be assessed via clinical interview and judgment. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine dependence-induced plasticity and is thus contingent on the presence of nicotine dependence. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to smoker/nicotine user status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml.
. For the treatment and non-treatment seeking groups, must be willing to attempt an acute abstinence period lasting approximately 48 hours.
. For the treatment seeking group, be actively seeking treatment for nicotine cessation and willing to engage in 12-weeks of treatment involving weekly counseling sessions, as well as follow-up imaging and behavioral assessments following treatment onset.
. For the ex-smoker group, must have smoked approximately 8 or more cigarettes per day for at least 1 year, and have remained abstinent continuously for at least the last 12 months. Justification: While serum cotinine level has been shown to be a more accurate measure of cigarette smoking than CPD \[85c\], it is impossible in the current design to collect retroactive serum cotinine levels from exsmokers. Instead, CPD must be equated with the urine cotinine levels of current treatment and nontreatment seeking groups. The low-end cotinine level for the inclusion of smokers/vapers in this protocol is about 200 ng/mL. In adult smokers, a nicotine intake of approximately 1 mg can be estimated from a blood cotinine level of 12.5 ng/mL) \[85d\]. Thus, to have achieved a blood cotinine level of 200ng/mL, ex-smokers would have to self-report consumption of 16 mg of nicotine per day which equates to approximately 8 CPD (0.36-2.62 mg nicotine yield per cigarette \[85e\]. Given these calculations, the inclusion criterion for the ex-smoker group has been lowered to 8 CPD. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to non-smoker status for the specific test being used, typically corresponding to a urine cotinine under about 20 ng/ml, CO \< 6.
. For the non-smoking/vaping control group, less than 20 times of lifetime use of nicotine containing products and vaping of non-nicotine containing products, none in past year and no history of daily nicotine use. Justification: Minimal nicotine exposure in the control group is required to assess differences between controls and the nicotine groups. Assessment tool(s): Self-report, commercial urine cotinine test corresponding to non-smoker status for the specific test being used, typically corresponding to a urine cotinine under about 20 ng/ml, CO \< 6.
.3 Exclusion criteria:
. are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.