PET Imaging of Nicotinic Acetylcholine Receptors

Healthy Volunteers Clinical Trial

Official title: PET Imaging of Nicotinic Acetylcholine Receptors With 2-[18F]F-A-85380-Injection, Initial Evaluation of Radiotracer in Human Volunteers

Status Completed

Clinical Trial Summary

Background:

• Central nicotinic acetylcholine receptors (nAChRs) are the primary target for the action of nicotine. In addition to being involved in tobacco dependence, they are also involved in a variety of brain disorders, including Alzheimer's and Parkinson's diseases. Researchers are interested in developing better ways to study the action of nAChRs to improve treatments for smoking cessation and other problems affected by these receptors. These new study methods may involve different radiotracers, which are drugs that can help show brain activity during positron emission tomography (PET) scanning.

Objectives:

• To evaluate the feasibility of using a radiotracer, 2-[18F]F-A-85380, in PET scanning of the brain.

Eligibility:

• Healthy volunteers between 21 and 45 years of age who do not use tobacco.

Design:

• Participants will be asked to avoid consuming alcohol or using a number of over-the-counter medications, including antihistamines, cough medicines, and nasal decongestants, for 5 days before the study day. Participants provide urine and breath samples at the start of the study to be tested for chemicals that may interfere with the study.

• Participants will visit the clinical center the morning of the day before the scanning session to provide blood and urine samples as required. Participants will return and be admitted for an overnight stay later that afternoon or evening.

• On the day of the study, participants will receive a single dose of the radiotracer 2-[18F]F-A-85380, and will have a series of PET scans over the next 7 hours and provide blood samples during that time. Participants will spend that night at the clinical center and leave on the morning after the end of the study.

• Participants will return for follow-up visits 2 weeks and 1 month after the end of the study.

Clinical Trial Description

Background: Central nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions and have been implicated in the pathophysiology of Alzheimer's and Parkinson's diseases, other CNS disorders (Tourette's syndrome, epilepsy, etc.), and nicotine dependence. These receptors are the primary target for the action of nicotine, which is believed to cause tobacco dependence. The availability of a suitable agent that could image nAChRs with PET in humans would allow scientists to monitor the nAChRs in vivo for the purpose of determining their roles in the pathogenesis of neurodegenerative diseases and nicotine dependence.

Scientific Goals: The immediate goal of the proposed study is to evaluate the feasibility of using a radiotracer, 2-[18F]F-A-85380, developed by scientists in the NIDA Brain Imaging Center for external imaging of nAChRs in the human brain.

Study Population: Healthy adult participants, males and females between 21 and 45 years of age, will be recruited for this study. The goal is to complete studies of 7 male and 7 female subjects.

Experimental Design and Method: After being medically cleared and giving informed consent, participants will receive a single dose of the radiotracer, 2 [18F]F A 85380-Injection, and will undergo a series of PET scans acquired over the next 7 hours after the injection. The PET scans will be used to determine the time course of the distribution of the injected radioactivity in those organs expected to receive the highest radiation exposure and in the brain.

Benefits to participants and/or society: This protocol will provide no direct benefits to the research participants other than routine medical screening and attention from the research staff. The knowledge gained in this study may lead to the availability of an agent for external monitoring of nAChRs using PET. This agent would be a valuable tool for determining the role of nAChRs in the pathogenesis of neuropsychiatric diseases, including nicotine dependence and for developing medications for diseases that respond to nicotinic agonists.

Risks to participants: There is some risk attendant to the PET scans in general, involving exposure to radiation, arterial catheterization and venous catheterization. In addition, there is risk related to the administration of this radiopharmaceutical, as it will be given to humans for the first time in this study. Medical supervision will be provided throughout the study. A plan for monitoring potential side effects of this radiotracer is given. ;

Related Conditions & MeSH terms

• Healthy Volunteers
• Nicotine Dependence
• Pharmacokinetics
• Tobacco Use Disorder

• NCT number: NCT01046513
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: N/A
• Start date: August 31, 2007
• Completion date: September 28, 2011