Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity
| Status: | Recruiting |
|---|---|
| Conditions: | Smoking Cessation, Tobacco Consumers |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 3/10/2019 |
| Start Date: | May 31, 2013 |
| End Date: | December 31, 2019 |
| Contact: | Elliot Stein, Ph.D. |
| Email: | estein@mail.nih.gov |
| Phone: | (443) 740-2650 |
Multimodal Neuroimaging Genetic Biomarkers of Nicotine Addiction Severity
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.
- 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.
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.
Study population: Four groups will be studied: target group of treatment seeking smokers;
nontreatment seeking current smokers; never smokers and former smokers. We estimate that we
will need n=50/group 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
e-cigarettes (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 seeking smoker comparison group will be scanned twice; at
baseline (scan 1) and at peak withdrawal (scan 2). Each of the non-smoking comparison groups
(non- 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 e-cigarettes and smoking and genetic markers of
nicotine addiction and relapse susceptibility.
severity that may be useful in predicting success in smoking cessation and in development of
new smoking cessation treatment targets.
Study population: Four groups will be studied: target group of treatment seeking smokers;
nontreatment seeking current smokers; never smokers and former smokers. We estimate that we
will need n=50/group 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
e-cigarettes (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 seeking smoker comparison group will be scanned twice; at
baseline (scan 1) and at peak withdrawal (scan 2). Each of the non-smoking comparison groups
(non- 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 e-cigarettes and smoking and genetic markers of
nicotine addiction and relapse susceptibility.
- 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.
We found this trial at
1
site
6001 Executive Boulevard, Room 5213
Baltimore, Maryland 20892
Baltimore, Maryland 20892
301-443-1124
Phone: 800-535-8254
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