Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 360
• Participant gender: Both

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute on Drug Abuse (NIDA)
• Treatments: Nicotine
• Last Updated: 2016-12-01

Criteria

• INCLUSION CRITERIA:

All participants must:

1. Be between the ages of 18-60. Be right-handed.

2. Be in good health.

3. Be free of active DSM-IV abuse/dependence, or dependence in partial remission, on alcohol or any drug except nicotine. Past active dependence is acceptable provided it is at least five years in the past. Those with past dependence on substances other than alcohol or marijuana may not have any current use (past 6 months) of the substance on which they were dependent. Individuals with past dependence on either alcohol or marijuana who report current use of the previously dependent substance may be included, provided they do not currently meet any criteria for dependence, with the exception of tolerance.

4. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to abstain from caffeine 24hrs before each session.

5. For the treatment and non-treatment seeking smoker groups, must have a urine cotinine level of greater than or equal to 4 and have been smoking consistently for at least one year. For lighter smokers (less than 10 cpd), this is defined as smoking at their current level or more for at least the past year (excluding any quit attempts in the last year). For heavier smokers (more than 10 cpd), they must have been smoking at least an average of 10 cpd 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 dependent smokers. Urine cotinine level provides a biomarker that does not rely on self-report/memory. Quit attempts will be assessed via clinical interview and judgment.

6. For the treatment seeking group, be actively seeking treatment for smoking cessation and willing to engage in 12-weeks of treatment involving nicotine substitution (e-cigarettes) and weekly counseling sessions, as well as follow-up imaging and behavioral assessments following treatment onset.

7. For the treatment seeking group, following discontinuaiton of regular cigarette smoking, be willing to attempt to use an e-cigarette for approximately 5 weeks prior to abstinence from all nicotine products.

8. For the non-smoking control group, less than 20 cigarettes lifetime, none in past year and no history of daily smoking.

EXCLUSION CRITERIA:

1. 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.

2. have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time.

3. have HIV or Syphilis.

4. regularly use any prescription (e.g., antidepressants, 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.

5. have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor.

6. have any current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders, or substance-induced psychiatric disorders, or any current suicidal ideations or currently under antidepressant or antipsychotic medication treatment. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion.

7. Are cognitively impaired or learning disabled.

8. have significant cardiovascular or cerebrovascular conditions.

9. have any other major medical condition that in the view of the investigators would compromise the safety of an individual during participation. The following lab values will result in exclusion from the study:

• Hemoglobin less than 10 g/dl

• White Blood Cell Count less than 2400/microl

• Liver Function Tests greater than 3X normal

• Serum glucose greater than 200 mg/dl

• Urine protein greater than 2 plus

• Serum creatinine greater than 2 mg/dl

• Estimated creatinine clearance less than 60ml/min

10. pregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period.