Quantitation of Human Cerebral Nicotinie Receptors With 2[18F]FA-85380 and PET Healthy Non-smokers and Ex-Smokers and in Heavy and Light Situational Smokers
|First Received Date ICMJE||December 19, 2009|
|Last Updated Date||November 19, 2011|
|Start Date ICMJE||July 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01038245 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Quantitation of Human Cerebral Nicotinie Receptors With 2[18F]FA-85380 and PET Healthy Non-smokers and Ex-Smokers and in Heavy and Light Situational Smokers|
|Official Title ICMJE||Quantitation of Human Cerebral Nicotinie Receptors With 2[18F]FA-85380 and PET Healthy Non-smokers and Ex-Smokers and in Heavy and Light Situational Smokers|
- Central nicotinic acetylcholine receptors (nAChRs) are primary targets 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 approaches to positron emission tomography (PET) scanning, which can show brain activity related to nAChRs.
- To evaluate appropriate and useful doses of radiotracers used in PET scanning of nAChRs in the brains of nonsmokers/former smokers, light smokers, and heavy smokers.
- Individuals between 18 and 50 years of age who fall into one of the following groups: (1) nonsmokers or former smokers who have not smoked for the past 2 years, (2) light/situational smokers, or (3) heavy smokers (at least 15 cigarettes/day for the past 2 years).
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 ability to quantitatively image nAChRs with PET in humans would allow scientists to monitor the nAChRs in vivo during nicotine dependence and smoking cessation and to determine the receptor occupancy by nicotine for different types of nicotine replacement therapy (NRT). Recently completed studies demonstrated the feasibility of imaging nAChRs in the human brain with 2[18F]FA-85380 and showed that each participant could receive up to 4 injections of 5 mCi/70 kg without exceeding dosimetry limits imposed by the FDA and the NIH Radiation Safety Committee.
Scientific Goal: The aims of the proposed study are 1) to compare the total volumes of distribution for 2[18F]FA-85380 and volumes of distribution for specific binding compartment (an estimate of nAChR densities) in brains of light and heavy smokers and 2) to develop a simplified PET procedure that is more comfortable for the human participants and that maintains the ability to accurately quantify nAChR binding in vivo.
Study Population: Healthy adult participants (non-smokers or exsmokers and light (situational) and heavy smokers), males and females between 18 and 50 years of age, will be recruited for this study. The goal is to complete studies of 12 controls (non-smokers or exsmokers), 12 light smokers and 12 heavy smokers.
Experimental Design and Method: After being medically cleared and giving informed consent, each participant will undergo up to three PET studies. In each study, the participant will receive a 5 mCi/70 kg dose of the radioligand, 2[18F]FA-85380-Injection. For one of the studies, the participants who smoke will receive nicotine by a nicotine patch (Nicoderm), applied approximately 4 h before the scan. The patch will be removed 12 h after it is applied. For two studies (one without and one with nicotine), participants who smoke will receive the radioligand as a bolus injection. Six of the participants who do not currently smoke (control group) will receive the radioligand as a bolus injection twice without nicotine either time. For the third study, all participants will receive the radioligand as a bolus injection followed by a continuous infusion (bolus injection/infusion combination). Six of the participants who do not currently smoke (control group) will receive the radioligand as a bolus plus infusion injection twice. For each study, a series of brain PET scans will be acquired for 8 h beginning at the time of the injection. The data from the PET scans without and with nicotine patch (smokers only) will be used to determine the total and non-specific accumulation of radioactivity in the brain. The data from the equivalent two PET scans for the controls will be used to determine the test-retest reliability of the measure. The data from the PET scans acquired from the bolus/infusion paradigm will be used to demonstrate the feasibility of a shorter scanning period for quantitation studies. It is anticipated that several of the participants will choose not to continue after the first scan. The study design accommodates this expectation.
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 dynamics of nAChRs in nicotine dependence and smoking cessation.
Risks to participants: There are risks related to the PET scans in general, involving exposure to radiation, arterial catheterization and venous catheterization. In addition, there are risks related to the administration of this radiopharmaceutical and from exposure to nicotine. Medical supervision will be provided throughout the study. A plan for monitoring potential side effects of this radiotracer is given.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Nicotine Addiction|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||72|
|Estimated Completion Date||November 2011|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 50 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01038245|
|Other Study ID Numbers ICMJE||999903383, 03-DA-N383|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute on Drug Abuse (NIDA)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||November 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP