Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity

NCT01867411 | Completed

• 2 other identifiers: 99991348513-DA-N485
• Study Type: observational
• Target: 159
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nicotine Dependence

Keywords

Smoking Cessation; fMRI; e-Cigarettes; Natural History

Outcome Measures

Primary Outcomes (6)

• Change in BOLD signal and functional connectivity related to task parameters, between drug conditions (i.e. on and off nicotine) and between groups

  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 nicotine withdrawal, in particular those related to anhedonia, negative affect, cognitive control and impulsive decision making.

  each scan visit

• Genetic and epigenetic data

  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.

  each scan visit

• Resting state MRI at follow-up

  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 (4 weeks, 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?

  each scan visit

• Behavioral performance on each task

  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.

  each scan visit

• Self-reported craving, withdrawal symptoms & mood/affect

  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.

  each scan visit

• Smoking status at 4wks, 3, 6 and 12 months.

  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 a standard 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.

  each scan visit

Secondary Outcomes (2)

• 2) Structural MRI and DTI data

  each visit

• 1) Ratings and scores on self-report characterization measures

  each visit

Study Arms (4)

ex-smokers

former smokers who have quit

never smokers/vapers

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

No preferences in participant recruitment will be made on the bases of gender, race, or ethnic background. Efforts will be made to avoid participant distribution bias such that if skewing is noted, subjects in the over-represented group may temporarily be excluded from the study until additional participates from under-represented groups can be established. Efforts will be made to include minorities in proportion to their presence in the local population. The major metropolitan Baltimore area (Baltimore City, Baltimore County, Anne Arundel County, Howard County) consists of 64% White, 32% Black or African American, 3% Asian, 0.3% American Indian and Alaska Native, 0.04% Native Hawaiian and Other Pacific Islander and 0.8% some other race (http://www.census.gov/ ). Of this population (any race), 2% are Hispanic or Latino.

You may qualify if:

• All participants must:
• 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.
• 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.
• 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 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.

You may not qualify if:

• Participants will be excluded if they:
• 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.
• have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal
• have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV blood test if oral test is + and STS+ without adequate prior treatment
• regularly use any prescription (e.g., benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medication (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function, cardiovascular function, or neuronal-vascular coupling. Antidepressant use will be allowed if an individual is on a stable dose of an SSRI or SNRI for \~6 weeks. As needed, benzodiazepine use is also allowed, but the individual must test negative for benzodiazepines on the drug screen. Justification: The use of some medications may alter the fMRI signal and/or neural functions of interest in the current study. Consistent antidepressant use or infrequent use of benzodiazepines is unlikely to drive study-related changes in brain function. Allowing such medication use will also make it possible to study nicotine dependent individuals who continue to smoke despite receiving treatment for a mood disorder. Assessment tool(s): History and comprehensive urine drug screening to detect antidepressants, benzodiazepines, antipsychotics, anticonvulsants, and barbiturates.
• Have current major psychiatric disorders to include, but not limited to psychotic disorders, or substance-induced psychiatric disorders, or risk of suicide or currently on antipsychotic medication treatment. Individuals with current major depressive disorder (MDD) and related anxiety will be allowed if currently stable, as assessed by the MAI. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion. Justification: Psychiatric disorders involve the central neural system (CNS) and, therefore, can be expected to alter the fMRI measures being used in this study. However, mood disorders such as MDD are highly comorbid with nicotine dependence. Including this population will generate results that are more representative of nicotine dependent individuals. Assessment tool(s): Computerized SCID or M.I.N.I., Beck Depression Inventory, Beck Anxiety Inventory, Adult ADHD Self-Report Scales and clinical interview confirmation by clinician.
• Are cognitively impaired or learning disabled. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance. Cognitive impairment may affect one s ability to give informed consent. Assessment tool(s): History examination and validated IQ test, such as the Wechsler Abbreviated Scale of Intelligence (WASI) or Shipley-2. IQ estimate must be 80 or over.
• have significant cardiovascular, cerebrovascular, or respiratory conditions. Justification: Such conditions may alter blood flow, the fMRI signal and other autonomic signals, and increase risks associated with nicotine patch and/or e-cigarette use. Assessment tool(s): History and physical exam, including 12-lead EKG.
• i. Hemoglobin \< 10 g/dl
• ii. White Blood Cell Count \< 2400/ l
• iii. Liver Function Tests \> 3X normal
• iv. Serum glucose \> 200 mg/dl
• v. Urine protein \> 2+
• vi. Serum creatinine \> 2 mg/dl
• vii. Estimated creatinine clearance \<60ml/min

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking Cessation; Vaping

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior; Behavior; Smoking

Study Officials

• Amy C Janes, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2013
• First Posted: June 4, 2013
• Study Start: November 6, 2013
• Primary Completion: June 29, 2024
• Last Updated: June 5, 2026

Record last verified: 2025-12-15

Locations

US (1)