|First Submitted Date||June 11, 2008|
|First Posted Date||June 12, 2008|
|Last Update Posted Date||July 2, 2017|
|Start Date||June 6, 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
||The first goal of this study is to compare [11C]PBR28 and [11C](R)-PK 11195 as radioligands in the measurement of PBR in healthy human subjects. Our primary outcome measures will be the distribution volume and time stability of each radioligand.|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00696371 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
||The second goal is to identify non-binders, that is, subjects that do not demonstrate any binding to [11C]PBR28.|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||PET Imaging of Peripheral Benzodiazepine Receptors|
|Official Title||PET Imaging of Peripheral Benzodiazepine Receptors Using [11C](R)-PK 11195 and [11C]PBR28|
This study will use positron emission tomography (PET) to measure a receptor in the brain that is involved in inflammation. It will test two radioactive chemicals used in the procedure to see if the newer chemical, [(11)C]B, is as good or better than the older one, [(11)C]A, for measuring brain inflammation.
Healthy volunteers 18 years of age and older may be eligible for this study. Participants undergo an evaluation, [(11)C]A PET scan, [(11)C]B PET scan and magnetic resonance imaging (MRI), as follows:
Medical history and physical examination, blood and urine tests
This test uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud noises that occur during the scan.
In response to brain inflammation, microglia over-express the peripheral benzodiazepine receptor (PBR). Although peripheral organs such as the heart and kidney express PBR constitutively, the brain normally expresses PBR in low numbers. Increased PBR density in the brain therefore signifies a change from a normal state to an active, inflammatory state. Positron emission tomography (PET) imaging can quantify PBR density in vivo using radioligands that bind to PBR sites. One PBR-selective radioligand, [(11)C](R)-PK 11195, has been used to identify areas of brain inflammation in patients with various neurological diseases. Unfortunately, [(11)C](R)-PK 11195 has several limitations, including low specific signal. A recently developed radioligand, [(11)C]PBR28, has higher specificity than [(11)C](R)-PK 11195 for PBR in animal studies. No study to date has compared [(11)C]PBR28 to [(11)C](R)-PK 11195 in human subjects.
In early clinical studies using [(11)C]PBR28, 4 of 32 healthy human subjects had complete absence of radioligand binding, even in peripheral organs that constitutively express PBR. One of these non-binders had specific binding of PBR28 on an in vitro assay using peripheral lymphocytes. We do not know why some subjects have [(11)C]PBR28 binding while others do not. We also do not know why one non-binder had positive in vitro binding and negative in vivo binding on PET imaging. No study has reported absent binding with [(11)C](R)-PK 11195. In order to better understand the phenomenon of non-binding, we need to obtain [(11)C](R)-PK 11195 PET scans in subjects that are [(11)C]PBR28 non-binders.
This protocol will study a total of 30 healthy human volunteers.
Fifteen subjects will undergo PET imaging with [(11)C]PBR28 and [(11)C](R)-PK 11195 using arterial blood sampling for fully quantitative image analysis. These subjects may have dedicated brain PET imaging or whole body PET imaging.
Fifteen subjects will undergo PET imaging with [(11)C]PBR28 and [(11)C](R)-PK 11195 without arterial blood sampling. These subjects will have whole body PET imaging.
All subjects will have in vitro PBR28 binding assays performed.
Our primary outcome measures will be the distribution volume and time stability of each radioligand. We also wish to determine if subjects with absent [(11)C]PBR28 binding also have absent [(11)C](R)-PK 11195 binding. The presence or absence of [(11)C]PBR28 and [(11)C](R)-PK 11195 binding will be evaluated in brain and in peripheral organs. Lastly, we will measure in vitro binding of PBR28 by performing binding assays using peripheral blood cells.
|Study Design||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Estimated Completion Date||August 19, 2014|
|Primary Completion Date||Not Provided|
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||080158
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )|
|Study Sponsor||National Institute of Mental Health (NIMH)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||August 19, 2014|