Conditions: Nicotine Dependence
Keywords: Nicotine, SPECT, vaccine, receptor
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 14
Healthy volunteers: yes

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.

Arms:
arm 1: There is only one arm to the study. All subjects will receive NicVax, \[123I\]5-I-A-85380,and Nicotine bitartrate.

Interventions: intervention 1: NicVAX intervention 2: [123I]5-IA-85380 intervention 3: Nicotine bitartrate
Intervention descriptions: intervention 1: 1.0 mL of Nicotine Conjugate Vaccine(x4), I.M. at 3 week intervals between SPECT studies intervention 2: up to 10 mCi of \[123I\]5-IA-85380, I.V. on each of two SPECT Scan days intervention 3: 0.5-1.5 mg of Nicotine bitartrate, I.V. on each of two SPECT Scan days

Protocol document: