Nicotinic Receptor Levels After Stopping Smoking

NCT01704573 | Completed

• 2 other identifiers: 812051P50CA143187
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine.

Conditions

Nicotine Addiction

Keywords

PET Scan

Outcome Measures

Primary Outcomes (1)

• Change in α4β2* nAChR binding potential

  This study uses a mixed design. A within-subject positron emission tomography (PET) study comparing α4β2\* nAChR availability, using 2-\[18F\]FA PET imaging, at two timepoints (1) during smoking as usual; and (2) after 24 hours of overnight abstinence. The order of the PET scans will be counterbalanced across subjects to prevent order effects that could bias the study results. Nicotine metabolite ratio (NMR) serves as the between-subject factor. The minimum amount of time between scans will be separated by one week. The maximum amount of time allowable between scans will be 4 weeks.

  Week 1 and up to Week 5

Secondary Outcomes (2)

• Cigarette craving

  Week 0, Week 1, and up to Week 5

• Behavioral Performance on cognitive tasks

  Week 1 and up to Week 5

Study Arms (1)

NMR by abstinence status

This study uses a mixed design with one between-subject factor (NMR: continuous variable) and one within-subject factor (session: 24 hours abstinent vs. smoking as usual) to examine NMR by abstinence status interactions on α4β2\* nAChR availability using 2-\[18F\]-fluro-3-\[2(S)-2-azethidinylmethoxy\]-pyridine (2-\[18F\]FA) PET imaging. Subjects will participate in two one-hour PET sessions: a) after smoking as usual (smoking exposure standardized) and b) the other following 24 hours of smoking abstinence. All participants who complete both PET scans will also complete an anatomical MRI scan.

Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine

Interventions

2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine DRUG

The study will be performed using an Investigational New Drug (IND) Application for the 2-\[18F\]FA radioligand. The 2-\[18F\]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us to measure the amount of light that 2-\[18F\]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region. 2-\[18F\]FA (radiotracer) is investigational, which means it is not approved by the United States Food and Drug Administration (FDA) for the way that it is being used in this research study. For this reason, we have received approval for all procedures in the current study including the use of 2-\[18F\]FA from the FDA.

Also known as: 2-[18F]FA, 2-FA

NMR by abstinence status

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10 cigarettes per day for at least 6 months will be the target population for the study. Participants will first be screened over the phone and then complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an MRI scan. 6 smokers who have completed the study and have agreed to be re-contacted for future studies will be invited to participate in an additional procedure. Participants will be screened over the phone and complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 1 PET scan.

You may qualify if:

• Ages 18 to 65 years old.
• Smoke 10 cigarettes per day for the previous 6 months.
• Weigh less than 300lbs (due to limitations of the PET and MRI scanners).

You may not qualify if:

• Smoking behavior:
• Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months.
• Provide a CO reading of less than 10 ppm at medical screening.
• Alcohol/Drugs:
• History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants).
• Positive drug screen at any of the sessions (see page 8 for list of drugs and/or contra-indicated medications).
• Current alcohol consumption that exceeds 25 standard drinks/week.
• Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 at any session.
• Medical:
• Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a serum pregnancy test at the medical screening session and urine pregnancy tests at the two PET scans and MRI scan.
• Women of child-bearing age must agree in writing to use an approved method of contraception or agree to abstain from sexual intercourse
• History or current diagnosis of the following psychiatric diagnoses identified by the MINI (Mini International Neuropsychiatric Interview) such as psychosis, bipolar disorder, schizophrenia, major current depression, or any Axis 1 disorder
• Self-report of serious or unstable disease within the past 6 months (e.g., cancer \[except melanoma\], HIV/AIDS, stroke, angina, coronary disease, heart attack).
• History of epilepsy or a seizure disorder.
• Any medical or neurological condition that might interfere with the distribution of the radiotracer as determined by the study M.D.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Pfizer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• CIRNA website

Biospecimen

Retention: SAMPLES WITH DNA

Two saliva samples will be collected at the medical screening session. A 6ml saliva sample will be used for nicotine metabolite ratio (NMR) estimation, and a 2ml saliva sample for DNA extraction (using an Oragene collection kit).

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Caryn Lerman, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2012
• First Posted: October 11, 2012
• Study Start: October 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 16, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)