- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02191267
Tau Imaging of Chronic Traumatic Encephalopathy
Chronic traumatic encephalopathy (CTE) is a progressive degenerative brain disease with symptoms that include memory loss, problems with impulse control, and depression that can lead to suicide. As the disease progresses, it can lead to dementia. Currently CTE can only be diagnosed postmortem where an over-accumulation of a protein called tau is observed. There is now a new experimental measure that makes it possible, for the first time, to measure tau protein in the living human brain using a novel positron emission tomography (PET) ligand, [F-18] AV-1451 (aka, [18F]-T807).
The main objective of this study is to use a novel PET approach to measure tau accumulation in the brain. The presence of CTE at autopsy in deceased National Football League (NFL) players has been well documented. Accordingly, we will conduct this study in a group of retired NFL players who have clinical symptoms of CTE and are suspected of having CTE based on high levels of tau in their spinal fluid and abnormalities seen on research brain scans. We will compare them with a control group of former elite level athletes who have not experienced any brain trauma, deny any clinical symptoms, and who have completely normal spinal fluid tau and amyloid levels, and brain scans. We will also include a group of subjects with AD. All participants will be recruited from ongoing studies, headed by the Partnering PI of this proposal, Dr. Robert Stern, at the Boston University Center for the Study of Traumatic Encephalopathy and the Alzheimer's Disease Center. We will use both a beta amyloid PET scan ([18F]-florbetapir) and a tau PET scan ([18F]-T807) on consecutive days. With the beta amyloid scan we expect little or no evidence of amyloid in the NFL players with presumed CTE, and no evidence of amyloid in the control group of athletes with no history of repetitive brain trauma. In contrast we expect to see beta amyloid accumulation in the AD patient brains. With the new tau ligand, we expect that the NFL players with presumed CTE will show elevated levels of tau protein in the brain, which will not be observed in athletes without a history of brain trauma, but which will be seen in the AD patients' brains.
Another goal is to use the latest MRI technologies to develop specific tau imaging biomarkers that correlate with the PET and spinal fluid tau measures but without the radiation of PET or invasiveness of spinal taps. The development of these surrogate imaging markers of tau, is critically important to diagnosing CTE. This in turn will lead to studies relevant to treatment and prevention of this devastating disease. Finally, as an exploratory method of examining possible genetic risk for CTE, we will also use cutting edge genetic analysis of blood samples from subjects in this proposal and compare tau load, measured by PET tau ligand uptake and cerebrospinal fluid (CSF) p-tau level, with a measure of genetic susceptibility to tau load, referred to as the genetic risk score for tau.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Brigham and Women's Hospital
-
Boston, Massachusetts, United States, 02118
- Boston University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Presumed CTE Group (includes 20 former NFL players who will have already participated in the NIH-funded R01 "DETECT" (Diagnosis and Evaluation of Traumatic Encephalopathy with Clinical Tests) study (Stern, PI; Shenton, Neuroimaging Site PI). Eligibility criteria for presumed CTE group and the control group are based on findings from the DETECT study.
Inclusion Criteria:
- significant cognitive impairment (and impairment in at least one of the following):
- behavioral (e.g., impulsivity, aggression),
- mood (e.g., elevated depression measures, elevated suicidality),
- and/or motor (e.g., impairments evidenced in neurological examination;
- demonstrated abnormalities on svMRI, DTI, or MRS
Exclusion Criteria:
- weight > 350 lbs
- known metallic implants preventing MRI
- history of stroke
- non-English speaking
- significant vision or hearing impairment
- unable to provide written informed consent
Control Group (comprised of 5 male participants selected from 50 control subjects in the DETECT study).
Inclusion Criteria:
- no history of mTBI or exposure to repetitive brain trauma
- normal functioning on DETECT clinical measures
- no abnormalities on svMRI, DTI, or MRS
Exclusion Criteria:
- weight > 350 lbs
- known metallic implants preventing MRI
- history of stroke or other neurological disease
- non-English speaking
- significant vision or hearing impairment
- AD Dementia Group (comprised of 5 male participants recruited from the BU Alzheimer's Disease Center (ADC) Clinical Core Registry (Dr. Stern, PI).
Inclusion Criteria:
- diagnosis of Dementia due to AD using the NIA-AA (National Institute on Aging-Alzheimer's Association) criteria
- Clinical Dementia Rating Global Score of 1.0,
- a positive florbetapir PET study,
- CSF p-tau/Aβ consistent with AD.
Exclusion Criteria:
- history of TBI, mTBI or or exposure to repetitive brain trauma
- weight > 350 lbs
- known metallic implants preventing MRI
- history of stroke or other neurological disease
- non-English speaking
- significant vision or hearing impairment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Presumed CTE Group
Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans, and Genetic Analysis for Genetic Risk Score for Tau.
|
[F18]-T807 PET Scan to measure tau deposition in the brain.
Other Names:
[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Other Names:
Two scans (structural, diffusion tensor imaging, and susceptibility weighted imaging scanned as part of one MR protocol, and a one-dimensional and two-dimensional spectroscopy examination as part of the other MR protocol.
Other Names:
DNA will be extracted from previously acquired and de-identified frozen blood specimens using a standard protocol (Gentra Puregene Kit, Qiagen 158422).
Genotyping will be performed using the iPLEX Sequenom MassARRAY platform and samples will be genotyped for single nucleotide polymorphisms (SNPs) associated with the deposition of neurofibrillary tangles.
|
Experimental: Control Group
Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans.
|
[F18]-T807 PET Scan to measure tau deposition in the brain.
Other Names:
[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Other Names:
Two scans (structural, diffusion tensor imaging, and susceptibility weighted imaging scanned as part of one MR protocol, and a one-dimensional and two-dimensional spectroscopy examination as part of the other MR protocol.
Other Names:
|
Experimental: AD Dementia Group
Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans
|
[F18]-T807 PET Scan to measure tau deposition in the brain.
Other Names:
[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
Other Names:
Two scans (structural, diffusion tensor imaging, and susceptibility weighted imaging scanned as part of one MR protocol, and a one-dimensional and two-dimensional spectroscopy examination as part of the other MR protocol.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tau Protein Uptake..
Time Frame: Day 1 - of 2 day study.
|
Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr).
Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes.
SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.
|
Day 1 - of 2 day study.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Beta-Amyloid (Aβ) Protein Uptake.
Time Frame: Day 2 - of 2 day study.
|
Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions.
Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir.
SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.
|
Day 2 - of 2 day study.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Martha E. Shenton, Ph.D., Brigham and Women's Hospital
Publications and helpful links
General Publications
- Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.
- Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014P000035
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Traumatic Encephalopathy
-
Tianjin Medical UniversityTianjin Medical University General HospitalRecruitingChronic Traumatic Encephalopathy | Traumatic Encephalopathy, Chronic | Traumatic; Encephalopathy, PostcontusionalChina
-
University of ArizonaCompletedTraumatic Brain Injury (TBI) | Chronic Traumatic Encephalopathy (CTE)United States
-
Avid RadiopharmaceuticalsCompletedChronic Traumatic EncephalopathyUnited States
-
University of California, Los AngelesWithdrawnSuspected Chronic Traumatic Encephalopathy (CTE) or Traumatic Encephalopathy Syndrome (TES) | Suspected Alzheimer's Disease (AD)
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Koninklijke Nederlandse VoetbalBond (KNVB)Not yet recruitingConcussion, Mild | Neurodegeneration | Head Injury, Minor | CTE - Chronic Traumatic Encephalopathy
-
Boston UniversityMayo Clinic; National Institute of Neurological Disorders and Stroke (NINDS); NYU Langone Health and other collaboratorsCompleted
-
Robert W. Alexander, MD, FICSWithdrawnConcussion, Mild | Concussion, Brain | Concussion, Severe | Concussion, Intermediate | Traumatic Encephalopathies, ChronicUnited States
-
University Hospital, Strasbourg, FranceRecruitingTraumatic Chronic EncephalopathyFrance
-
National Institute of Mental Health (NIMH)Completed
-
University Health Network, TorontoThe Weston A. Price FoundationRecruitingChronic Traumatic EncephalopathyCanada
Clinical Trials on [F18]-T807
-
Avid RadiopharmaceuticalsTerminatedAlzheimers Disease | ADUnited States
-
Avid RadiopharmaceuticalsCompletedAlzheimer's DiseaseUnited States
-
Avid RadiopharmaceuticalsCompletedCorticobasal Degeneration | Progressive Supranuclear PalsyUnited States
-
Avid RadiopharmaceuticalsCompletedAlzheimer's DiseaseUnited States
-
Samuel GandyCompletedTraumatic Brain Injury | Mild Cognitive Impairment | Chronic Traumatic EncephalopathyUnited States
-
University of North Carolina, Chapel HillBoston Children's Hospital; Medical College of Wisconsin; National Football LeagueEnrolling by invitation
-
Avid RadiopharmaceuticalsCompleted
-
Avid RadiopharmaceuticalsCompleted
-
Avid RadiopharmaceuticalsCompleted
-
Avid RadiopharmaceuticalsCompleted