PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [11C]PBR28 in Frontotemporal Dementia
|First Received Date ICMJE||February 10, 2008|
|Last Updated Date||October 8, 2016|
|Start Date ICMJE||January 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Outcome measures will be the amount of [11C]PBR28 binding in the brain in FTD patients and in healthy controls.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00613119 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||We will quantify the radioligand's brain uptake, washout, plasma clearance, and distribution volume using compartmental modeling.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [11C]PBR28 in Frontotemporal Dementia|
|Official Title ICMJE||PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [11C]PBR28 in Neurological Disorders|
This study will use positron emission tomography (PET) imaging to measure a receptor in the brain that is involved in inflammation. Certain neurological disorders, possibly including frontotemporal dementia (FTD), are associated with increased inflammation in the brain. This study may help elucidate the relationship between FTD and inflammation.
Patients with FTD and healthy volunteers who are 35 years of age or older may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, and blood and urine tests.
Participants undergo the following procedures:
Abnormal immune responses and inflammatory mechanisms have been implicated in the pathogenesis of certain neurodegenerative diseases. Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by focal atrophy of the frontal and temporal lobes. Evidence supports the presence of inflammation in FTD; however, the relationship between inflammation and FTD pathogenesis is poorly understood. In addition, there is evidence of inflammation in temporal lobe epilepsy (TLE), a condition characterized by seizures originating from the mesial temporal lobe.
In response to brain inflammation, microglia are activated and over-express the peripheral benzodiazepine receptor (PBR). In normal conditions, PBR is expressed in low numbers. Measuring PBR density can identify areas of brain inflammation, because activated microglial cells in these areas express more PBR than microglial cells in resting conditions. Positron emission tomography (PET) imaging can quantify PBR density in vivo using radioligands that bind to PBR sites. One PBR-specific radioligand, [11C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195), has been used to identify areas of brain inflammation in patients with FTD. Unfortunately, [11C]PK11195 has several limitations, such as low brain uptake and low specific signal. A recently developed radioligand, [11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28), has higher affinity than [11C]PK11195 for PBR. [11C]PBR28 has never been used to study inflammation in FTD.
To further study brain inflammation in dementia and TLE, we wish to include patients with Alzheimer disease (AD) and TLE.
In this protocol, we wish to evaluate 20 patients with FTD, 50 100 patients with AD, 20 patients with TLE, and 30 55 healthy volunteers.
Subjects will undergo a dedicated brain PET with [11C]PBR28, as well as a brain MRI. In AD patients and controls, 11C PBR28 PET and MRI will then be repeated after an interval of one year but no more than 5 years.
Outcome measures will be the amount of 11C PBR28 binding in the brain in FTD patients, AD patients, TLE patients and in healthy controls. We will quantify the radioligand s brain uptake, washout, plasma clearance, and distribution volume using compartmental modeling. Distribution volume is proportional to the density of receptors and is equal to the ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma. 11C PBR28 binding will also be compared between baseline and follow-up scans to determine the change in binding related to evolution of AD pathology and that related to normal aging.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||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.
|Recruitment Status ICMJE||Completed|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||35 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|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||NCT00613119|
|Other Study ID Numbers ICMJE||080066, 08-M-0066|
|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||National Institute of Mental Health (NIMH)|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 2016|
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