Clinical trial NCT00996034: Nicotine Vaccination and Nicotinic Receptor Occupancy
Official title: 123I-5-IA SPECT Imaging of Nicotinic Receptors and Effects of Nicotine Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nicotine Dependence
Keywords: Nicotine, SPECT, vaccine, receptor
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Nabi Biopharmaceuticals
name: National Institute on Drug Abuse (NIDA)
First posted: 2009-10-16
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean of the Average Nicotine Binding % at Scan 1 and Scan 2
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: West Haven
country: United States
facility: Veterans Association Connecticut Hospital System
state: Connecticut
Study officials:
affiliation: Yale University
name: Irina Esterlis, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.