Nicotine Vaccination and Nicotinic Receptor Occupancy

Nicotine Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996034
• Other study ID #: 0804003655
• Secondary ID: R21DA024388
• Status: Completed
• Phase: Phase 2
• First received: October 14, 2009
• Last updated: November 19, 2015
• Start date: September 2009
• Est. completion date: February 2011

Study information

• Verified date: November 2015
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Nicotine Dependence

Intervention

Biological:
• NicVAX
1.0 mL of Nicotine Conjugate Vaccine(x4), I.M. at 3 week intervals between SPECT studies

Radiation:
• [123I]5-IA-85380
up to 10 mCi of [123I]5-IA-85380, I.V. on each of two SPECT Scan days

Drug:
• Nicotine bitartrate
0.5-1.5 mg of Nicotine bitartrate, I.V. on each of two SPECT Scan days

Locations

Country	Name	City	State
United States	Veterans Association Connecticut Hospital System	West Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	Nabi Biopharmaceuticals, National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No