Nicotine Vaccination and Nicotinic Receptor Occupancy

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.

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.

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

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.

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.

Esterlis I, Hannestad JO, Perkins E, Bois F, D'Souza DC, Tyndale RF, Seibyl JP, Hatsukami DM, Cosgrove KP, O'Malley SS. Effect of a nicotine vaccine on nicotine binding to beta2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers. Am J Psychiatry. 2013 Apr;170(4):399-407. doi: 10.1176/appi.ajp.2012.12060793.