Nicotine Dependence
Conditions
Keywords
Nicotine, SPECT, vaccine, receptor
Brief summary
This is a molecular imaging research study designed to examine how much nicotine gets into the brain before and after vaccination with NicVAX, a nicotine vaccine developed by Nabi Biopharmaceuticals. NicVAX (Nicotine Conjugate Vaccine) is an investigational vaccine designed as an aid to smoking cessation and long-term abstinence, as well as an aid to prevent relapses of a treated smoker. In this project we want to understand the degree to which NicVAX administration changes how much nicotine enters the brain in smokers.
Detailed description
The purpose of the present study is to examine the occupancy of brain β2-containing nicotinic acetylcholine receptors (β2-nAChR) by nicotine both at baseline and following administration of a nicotine vaccine. The number of brain β2-nAChR and the amount of nicotine occupancy both before and after vaccination will be measured using the nicotinic agonist \[123I\]5-IA-85380 (\[123I\]5-IA) and single photon emission computed tomography (SPECT). \[123I\]5-IA will be administered using the bolus plus constant infusion paradigm to smokers abstinent for 4-9 days (time period necessary for nicotine and pharmacological active metabolites to clear from brain). Three baseline SPECT images will be obtained after equilibrium has been reached (\ 6 hours into the \[123I\]5-IA infusion). Then, IV nicotine will be administered (0.5-1.5 mg/70 kg will be infused over 10 minutes). Following a series of 4 nicotine vaccine shots, the same procedure will be repeated for a second \[123I\]5-IA scan day. We hypothesize that occupancy of β2-nAChR will be significantly lower, and take longer to plateau, following nicotine vaccine administration.
Interventions
BIOLOGICALNicVAX
1.0 mL of Nicotine Conjugate Vaccine(x4), I.M. at 3 week intervals between SPECT studies
RADIATION[123I]5-IA-85380
up to 10 mCi of \[123I\]5-IA-85380, I.V. on each of two SPECT Scan days
DRUGNicotine bitartrate
0.5-1.5 mg of Nicotine bitartrate, I.V. on each of two SPECT Scan days
Sponsors
Nabi Biopharmaceuticals
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Current smoker who smokes at least 10-25 cigarettes a day * Good general health
Exclusion criteria
* Subjects with a pacemaker or other ferromagnetic material in body. * Prior exposure to NicVAX or any other nicotine vaccine. * Use of systemic steroids or other immunosuppressive agent * History of significant neurological, cardiovascular, hepatic, endocrine, renal, liver, psychiatric or thyroid illness * Cancer or cancer treatment in last 5 years * HIV infection * Use of varenicline (Chantix), bupropion (Wellbutrin, Zyban), mecamylamine (Inversin), within 30 days prior to administration of NicVAX and for the duration of the study. * Inability to fulfill all visits and examination procedures for approximately 20 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean of the Average Nicotine Binding % at Scan 1 and Scan 2 | 3 months | nAchR levels from baseline and after immunization with 3'-AmNic-rEPA (NicVAX=vaccine) SPECT images obtained in healthy control smoking subjects at baseline and after immunization with 3'-AmNic-rEPA (NicVAX=vaccine). nAchR levels will be determined by radioligand uptake in SPECT images. Means were calculated for all subjects at scan 1 and scan 2. |
Countries
United States
Participant flow
Recruitment details
Enrollment in to the study ended in Feb. 2011. Subjects were screened and recruited from the VA West Haven, CT.
Pre-assignment details
Several possible subject were not enrolled in to the study because of the exclusion/inclusion criteria, such as allergies to medications, high blood pressure, or SCID II diagnosis
Participants by arm
| Arm | Count |
|---|---|
| Healthy Smoker Healthy smokers with nicotine dependence
Nicotine bitartrate : 0.5-1.5 mg of Nicotine bitartrate, I.V. on each of two SPECT Scan days
\[123I\]5-IA-85380 : up to 10 mCi of \[123I\]5-IA-85380, I.V. on each of two SPECT Scan days
NicVAX : 1.0 mL of Nicotine Conjugate Vaccine(x4), I.M. at 3 week intervals between SPECT studies | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | withdrawn by PI | 1 |
Baseline characteristics
| Characteristic | Healthy Smoker |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 31.15 years STANDARD_DEVIATION 8.33 |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Mean of the Average Nicotine Binding % at Scan 1 and Scan 2
nAchR levels from baseline and after immunization with 3'-AmNic-rEPA (NicVAX=vaccine) SPECT images obtained in healthy control smoking subjects at baseline and after immunization with 3'-AmNic-rEPA (NicVAX=vaccine). nAchR levels will be determined by radioligand uptake in SPECT images. Means were calculated for all subjects at scan 1 and scan 2.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Smoker | Mean of the Average Nicotine Binding % at Scan 1 and Scan 2 | Scan 1 | 54.9 percentage of average nicotine binding | Standard Deviation 8.7 |
| Healthy Smoker | Mean of the Average Nicotine Binding % at Scan 1 and Scan 2 | Scan 2 | 49.1 percentage of average nicotine binding | Standard Deviation 10.1 |
Comparison: This is a comparison of scan 1 and scan 2p-value: <0.05ANOVA