Nicotine Dependence
Conditions
Brief summary
In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI).
Detailed description
phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects' nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated.
Interventions
Subjects received a single infusion of nicotine, 1.5 mg/70kg (New England Compounding Center, Framingham, MA), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.
OTHERSaline - placebo
Subjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.
Sponsors
National Institute on Drug Abuse (NIDA)
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence will be eligible for participation. * No evidence of clinically significant disease based upon complete medical history and physical examination by a qualified physician. * Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID). * Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function tests, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable. * Hematocrit levels ≥ 39% for males and ≥ 35% for females. * Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study day. * Normal ECG. * A Body Mass Index (BMI-ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18.0 and 27.0 for women and 21.4 to 29 for men. * Subjects must be able to read and understand instructions, as well as provide a valid informed consent.
Exclusion criteria
* Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence. * Participants with clinically significant medical disorders. * Women who are pregnant as determined by laboratory testing for serum beta hCG. * Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures. * Women with a mean BMI of outside the range 18.0-27.0 and men with a BMI outside the range 21.4-29.0. * Participants with ferromagnetic implants or other contraindications to fMRI * Cardiac pacemakers * Metal clips on blood vessels (also called stents) * Artificial heart valves * Artificial arms, hands, legs, etc. * Brain stimulator devices * Implanted drug pumps * Ear implants * Eye implants or known metal fragments in eyes * Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others) * Other metallic surgical hardware in vital areas * Certain tattoos with metallic ink * Transdermal patches (eg. Orthro Evra, Nicoderm CQ) * Metal IUD (s) * Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Nicotine Levels | 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion | Peak nicotine level in each participant |
| Number of Brain Regions With a Change in Brain Activity Relative to Saline | 40 minutes after infusion | PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History | 40 minutes after infusion | PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course controlling for smoking history (pack years). The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps. |
| Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine | 40 minutes after infusion | PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with smoking history (pack years) controlling for nicotine. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps. |
| Final Nicotine Levels | 30 minutes post-infusion | Final nicotine level in each participant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants. All participants were randomized to receive all interventions, so all participants are combined into one Arm/Group. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 26.5 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fagerström score | 6.0 units on a scale STANDARD_DEVIATION 1.3 |
| Pack-years | 11.2 pack-years STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Brain Regions With a Change in Brain Activity Relative to Saline
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Time frame: 40 minutes after infusion
Population: The data from three subjects were not included in the imaging results, one due to incomplete serum nicotine results, one due to a misalignment of the head in the scanner, which resulted in incomplete brain coverage, and one subject had a combination of excessive motion and abnormal anatomy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline | Increased BOLD Signal | 9 brain regions |
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline | Decreased BOLD Signal | 5 brain regions |
Primary
Peak Nicotine Levels
Peak nicotine level in each participant
Time frame: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion
Population: Peak nicotine levels were only measured during the nicotine study intervention. One participant had incomplete serum nicotine results and was not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Peak Nicotine Levels | 16.1 ng/ml | Standard Deviation 8 |
| Placebo | Peak Nicotine Levels | 0 ng/ml | Standard Deviation 0 |
Secondary
Final Nicotine Levels
Final nicotine level in each participant
Time frame: 30 minutes post-infusion
Population: One participant had incomplete serum nicotine results and was not included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine | Final Nicotine Levels | 8.2 ng/ml | Standard Deviation 2.2 |
| Placebo | Final Nicotine Levels | 0 ng/ml | Standard Deviation 0 |
Secondary
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with smoking history (pack years) controlling for nicotine. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Time frame: 40 minutes after infusion
Population: The data from three subjects were not included in the imaging results, one due to incomplete serum nicotine results, one due to a misalignment of the head in the scanner, which resulted in incomplete brain coverage, and one subject had a combination of excessive motion and abnormal anatomy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine | Increased BOLD Signal | 9 brain regions |
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine | Decreased BOLD Signal | 7 brain regions |
Secondary
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course controlling for smoking history (pack years). The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Time frame: 40 minutes after infusion
Population: The data from three subjects were not included in the imaging results, one due to incomplete serum nicotine results, one due to a misalignment of the head in the scanner, which resulted in incomplete brain coverage, and one subject had a combination of excessive motion and abnormal anatomy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History | Increased BOLD Signal | 9 brain regions |
| Nicotine | Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History | Decreased BOLD Signal | 4 brain regions |