Nicotine Vaccination and Nicotinic Receptor Occupancy

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

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.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Biological: NicVAX; Radiation: [123I]5-IA-85380; Drug: Nicotine bitartrate

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Veterans Association Connecticut Hospital System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); Nabi Biopharmaceuticals
• Investigators: Principal Investigator: Irina Esterlis, Ph.D., Yale University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): February 1, 2011
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (ESTIMATE): October 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 24, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Nicotine, SPECT, vaccine, receptor
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 0804003655; R21DA024388 (NIH)