Nicotine Vaccination and Nicotinic Receptor Occupancy

Study Overview
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Brief Summary
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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
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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.

Official Title
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123I-5-IA SPECT Imaging of Nicotinic Receptors and Effects of Nicotine Vaccine

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Biological: NicVAX
* Radiation: [123I]5-IA-85380
* Drug: Nicotine bitartrate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Smoker<br>There is only one arm to the study. All subjects will receive NicVax, [123I]5-I-A-85380,and Nicotine bitartrate. | Biological: NicVAX<br>* 1.0 mL of Nicotine Conjugate Vaccine(x4), I.M. at 3 week intervals between SPECT studies<br>* Other names: Nicotine Conjugate Vaccine;Radiation: [123I]5-IA-85380<br>* up to 10 mCi of [123I]5-IA-85380, I.V. on each of two SPECT Scan days<br>* Other names: 5-IA;Drug: Nicotine bitartrate<br>* 0.5-1.5 mg of Nicotine bitartrate, I.V. on each of two SPECT Scan days<br>* Other names: IV nicotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine, SPECT, vaccine, receptor