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Nicotine Vaccination and Nicotinic Receptor Occupancy

Phase 2
Completed
Conditions
Nicotine Dependence
Interventions
Biological: NicVAX
Radiation: [123I]5-IA-85380
Drug: Nicotine bitartrate
Registration Number
NCT00996034
Lead Sponsor
Yale University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
Inclusion Criteria
  • Current smoker who smokes at least 10-25 cigarettes a day
  • Good general health
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Healthy SmokerNicVAXThere is only one arm to the study. All subjects will receive NicVax, \[123I\]5-I-A-85380,and Nicotine bitartrate.
Healthy Smoker[123I]5-IA-85380There is only one arm to the study. All subjects will receive NicVax, \[123I\]5-I-A-85380,and Nicotine bitartrate.
Healthy SmokerNicotine bitartrateThere is only one arm to the study. All subjects will receive NicVax, \[123I\]5-I-A-85380,and Nicotine bitartrate.
Primary Outcome Measures
NameTimeMethod
Mean of the Average Nicotine Binding % at Scan 1 and Scan 23 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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Veterans Association Connecticut Hospital System

🇺🇸

West Haven, Connecticut, United States

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