Translocator Protein and Inflammation After Traumatic Brain Injury
|First Received Date ICMJE||March 6, 2012|
|Last Updated Date||November 27, 2013|
|Start Date ICMJE||January 2012|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Binding of [(11)C]PBR28.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01547780 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Neurocognitive assessment scores and clinical evaluations|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Translocator Protein and Inflammation After Traumatic Brain Injury|
|Official Title ICMJE||PET Imaging of Translocator Protein in Subjects With Traumatic Brain Injury|
- People with traumatic brain injury (TBI) often have inflammation in the brain. A protein called the translocator protein (TSPO) is often present with inflammation. Researchers want to see if a radioactive chemical known as [11C]PBR28 can be used to study TSPO and inflammation in the brain of people with TBI.
- To test whether [11C]PBR28 can be used to study changes in the brain after a traumatic brain injury.
Brain damage following traumatic injury (TBI) results from both direct (eg, mechanical injury to the brain and vasculature) and indirect mechanisms (eg, secondary mechanisms such as inflammation). While CT and MRI can help visualize the result of inflammatory processes in the brain for instance, the development of cerebral edema neither method can be used to document active inflammation itself. The translocator protein (TSPO), which is highly expressed in microglia and reactive astrocytes, has been used as a biomarker in positron emission tomography (PET) to identify active inflammatory processes. Recently, our laboratory developed PBR28, a new PET ligand that images TSPO with high levels of specific binding. We have successfully used PBR28 to investigate a number of brain disorders such as epilepsy, multiple sclerosis, and HIV infection with minor cognitive motor disorder, and are detecting neuroinflammation. The current protocol aims to explore whether PBR28 PET imaging can show changes in subjects with TBI who have shown MRI abnormalities in the acute phase and also in those who are in the chronic phase of TBI.
Study population: The following three groups will be studied:
TBI subjects who had brain injury within approximately 3 months and have exhibited MRI abnormalities consistent with TBI and who are enrolled in one of two protocols "Evaluation, Pathogenesis, and Outcome of Subjects with or Suspected Traumatic Brain Injury" (10-N-N122, PI Latour) or "Evaluation and Diagnosis of Potential Research Subjects with Traumatic Brain Injury (TBI), (11-N-0084, PI: Lawrence Latour). N = 20
TBI subjects who had brain injury more than approximately 5 month ago, are enrolled in 11-N-0084, and meet criteria of TBI established by CNRM. N = 20
Healthy age-matched volunteers. N = 20.
This is an exploratory study to determine whether PBR28 can detect the increased TSPO associated with neuroinflammation by scanning subjects who have shown MRI abnormalities in the acute phase. We also investigate whether PBR28 detects changes in the chronic phase as recently reported using an old ligand, PK 11195. Two groups of TBI subjects will be studied depending on their availability relative to the time of injury. To investigate changes in TSPO in the areas of MRI abnormalities in the acute phase, one group of TBI subjects (n = 20) will be studied who have shown TBI- related MRI abnormalities. These participants will have up to four PBR28 PET scans; one to two PET scans within approximately 10 days of head injury, a third PET scan approximately three months after injury, and a fourth scan approximately one year after the scan at ~three months. To study changes in TSPO in the chronic phase, another group of TBI subjects will be enrolled who had brain injury more than approximately 5 months but within 5 years ago and meet the criteria of TBI by CNRM. This separate group is included because some TBI subjects are being recruited by CNRM only sometime after the injury. The participants at the chronic phase will have one PET and one MRI scan. In addition to MRI data, for all TBI subjects, clinical information obtained in 10-N-N122 (only the acute phase) and 11-N-0084 (both acute and chronic phase) will be used to evaluate the utility of the PET data in order to better understand the pathology of TBI.
In this exploratory study to investigate the ability of PBR28 PET to detect increases in TSPO, the primary goal will be to measure the magnitude and variance of any increases observed in PBR28 binding in areas of inflammation following TBI. Those data may be used to design future studies with a larger sample size.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Intervention ICMJE||Radiation: PET
|Study Arm (s)||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||Recruiting|
|Estimated Enrollment ICMJE||40|
|Estimated Completion Date||May 2015|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Subjects with TBI:
Subjects with TBI eligible for participation in this research study must meet the following inclusion criteria. Depending on the timing of the availability of the subjects the following two groups will be studied. No subject will be enrolled in both group 1 and 2.
Group 1 Acute/subacute phase (n = 20)
Group 2 Chronic phase (n = 20)
Group 3 Healthy subjects.
Subjects with TBI for both groups 1 and 2 are not eligible for participation in this research study if any of the following conditions exist:
HEALTHY SUBJECTS ARE NOT ELIGIBLE FOR PARTICIPATION IN THIS RESEARCH IF ANY OF THE FOLLOWING CONDITIONS EXIST:
HIV positive subjects are considered healthy as long as he/she does not show neuological or psychiatric symptoms based on history and physical exams. Results of HIV test in both TBI subjects and healthy controls may help interpretation of the PET results. Statistical analysis: Analysis of date/study outcomes.
|Ages||18 Years to 70 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01547780|
|Other Study ID Numbers ICMJE||120063, 12-M-0063|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2013|
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