Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity
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|ClinicalTrials.gov Identifier: NCT01867411|
Recruitment Status : Recruiting
First Posted : June 4, 2013
Last Update Posted : July 7, 2022
- 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.
- 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.
- 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.
- 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.
|Condition or disease|
Objective: To develop a neuroimaging/genetic/epigenetic biomarker of nicotine dependence severity that may be useful in predicting success in smoking cessation and in development of new smoking cessation treatment targets. Further, by evaluating those who vape nicotine, findings will determine whether biomarkers differ between those who smoke or vape, allowing for the development of cessation
strategies that relate to preferred nicotine delivery.
Study population: Four groups will be studied: target group of treatment seeking smokers/vapers; nontreatment seeking current smokers/vapers; never smokers/never vapers and former smokers. We estimate that we will need n=50/subgroup completers to have sufficient power to develop the brain/genetics biomarkers.
Design: This study consists of a 4 group between/within subject design. The experimental group will proceed in 4 phases: Baseline (scan 1), peak withdrawal (scan 2), stable on nicotine replacement (scan 3), and complete abstinence (scans 4-6). Counseling will start after the first scan session and will generally continue weekly until scan 4 (about 12 weeks). After scan 4, therapeutic support will be
provided at least monthly via phone until completion of the protocol. The non-treatment seeker comparison group will be scanned twice; at baseline (scan 1) and at peak withdrawal (scan 2). Each of the non-nicotine user comparison groups (non-nicotine users and Ex-smokers) will be scanned only at baseline (scan 1). Genetic and epigenetic markers will be obtained in all groups.
Outcome measures: Network and multivariate pattern analysis, behavior on a decision making task and task based and resting state blood oxygen level-dependent (BOLD) activation in neural circuits relevant to nicotine addiction during fMRI scanning. Secondary outcomes include BOLD response comparisons between nicotine replacement and typical nicotine use and genetic markers of nicotine addiction and relapse susceptibility.
|Study Type :||Observational|
|Estimated Enrollment :||630 participants|
|Official Title:||Multimodal Neuroimaging Genetic Biomarkers of Nicotine Addiction Severity|
|Actual Study Start Date :||November 6, 2013|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2024|
former smokers who have quit
never smoked/vaped nicotine
non-treatment seeking smokers/vapers
smokers/vapers not interested in quitting nicotine
Treatment seeking smokers/vapers
smokers/vapers interested in quitting nicotine
- Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups [ Time Frame: each scan visit ]1)Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups: will provide important insight into the neurobiological mechanisms underlying acute and chronic nicotinewithdrawal, in particular those related to anhedonia, negative affect, cognitive control and impulsive decision making.
- Genetic and epigenetic data [ Time Frame: each scan visit ]2)Genetic and epigenetic data. These data will be included into the network and pattern classification models discussed above as features in the classifier. They will also be used as regressors, covariates or dichotomous variable in the above BOLD task analysis.
- Resting state MRI at followup [ Time Frame: each scan visit ]3)Resting state MRI at follow-up. Resting state MRI will be assessed between- and within- groups as a function of relapse status and time since last treatment visit at each of the follow-up time-points (4weeks, 3, 6 and 12 months). These data will be entered into the network and pattern classification models discussed above. This will allow us to address the following questions:i. What characteristics of rsFC are associated with treatment success (vs. failure)? ii. Are there characteristics of rsFC that vary as a function of time post-treatment in successfully abstinent individuals?
- Behavioral performance on each task [ Time Frame: each scan visit ]4)Behavioral performance on each of the tasks assessing working memory, attention, processing speed, inhibitory control processes, cognitive control, reward responsiveness, amygdala, striatal, and impulsive decision making (e.g., reaction time, error rate, hit rate, reward bias): will provide task-related parameters necessary for analysis of BOLD and resting state data. Performance data will function as a secondary outcome by providing behavioral validation of acute and chronic nicotine withdrawal effects.
- Self-reported craving, withdrawal symptoms & mood/affect [ Time Frame: each scan visit ]5)Self-reported craving, withdrawal symptoms and mood/affect: will be employed as regressors in the analysis of task and resting BOLD data. They will also provide the primary means of validating the acute nicotine withdrawal manipulation.
- Smoking status at 4wks, 3, 6 and 12 months. [ Time Frame: each scan visit ]6)Smoking status at 4 weeks, 3, 6 and 12 months: Smoking status (relapse vs. abstinent) at each of the follow-up time points will be based on 7-day point prevalence defined as no smoking (not even a puff) or use of any tobacco products for the past 7 days. This is astandard method of assessing abstinence and dichotomizing relapse status at follow-up. Whenever abstinence at follow-up is assessed in-person, self-reported abstinence will be corroborated with breath COand urine cotinine levels.
- 2)Structural MRI and DTI data [ Time Frame: each visit ]2)Structural MRI and DTI data
- 1) Ratings and scores on self-report characterization measures [ Time Frame: each visit ]1)Ratings and scores on self report characterization measures
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01867411
|Contact: Betty Jo Salmeron, M.D.||(443) email@example.com|
|Contact: Amy Janes, Ph.D.||(443) firstname.lastname@example.org|
|United States, Maryland|
|National Institute on Drug Abuse||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: Betty Jo Salmeron, M.D. 443-740-2651 email@example.com|
|Principal Investigator:||Amy Janes, Ph.D.||National Institute on Drug Abuse (NIDA)|