Tau Imaging of Chronic Traumatic Encephalopathy
1 other identifier
interventional
30
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2015
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 15, 2014
CompletedFirst Posted
Study publicly available on registry
July 16, 2014
CompletedStudy Start
First participant enrolled
January 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2016
CompletedResults Posted
Study results publicly available
May 17, 2018
CompletedMay 17, 2018
April 1, 2018
1.7 years
July 15, 2014
March 15, 2018
April 19, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Tau Protein Uptake..
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 Outcomes (1)
Beta-Amyloid (Aβ) Protein Uptake.
Day 2 - of 2 day study.
Study Arms (3)
Presumed CTE Group
EXPERIMENTALInterventions 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.
Control Group
EXPERIMENTALInterventions administered to the Control Group include: \[F-18\]-T807 PET Scan, \[F18\]-Florbetapir PET Scan, and MRI/MRS Scans.
AD Dementia Group
EXPERIMENTALInterventions administered to the AD Dementia Group include: \[F-18\]-T807 PET Scan, \[F18\]-Florbetapir PET Scan, MRI/MRS Scans
Interventions
\[F18\]-T807 PET Scan to measure tau deposition in the brain.
\[F18\]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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).
- no history of mTBI or exposure to repetitive brain trauma
- normal functioning on DETECT clinical measures
- no abnormalities on svMRI, DTI, or MRS
- weight \> 350 lbs
- known metallic implants preventing MRI
- history of stroke or other neurological disease
- non-English speaking
- significant vision or hearing impairment
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Brigham and Women's Hospitallead
- U.S. Army Medical Research and Development Commandcollaborator
- Boston Universitycollaborator
Study Sites (2)
Boston University Medical Center
Boston, Massachusetts, 02118, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
Related Publications (2)
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.
PMID: 22683529BACKGROUNDChien 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.
PMID: 23234879BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Exploratory aims including potential MRI and MRS biomarkers and genetic analysis for genetic risk score for Tau will also be analyzed but are not primary or secondary outcome measures.
Results Point of Contact
- Title
- Dr. Martha Shenton
- Organization
- Brigham and Women's Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Martha E. Shenton, Ph.D.
Brigham and Women's Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Psychiatry Neuroimaging Laboratory
Study Record Dates
First Submitted
July 15, 2014
First Posted
July 16, 2014
Study Start
January 1, 2015
Primary Completion
September 30, 2016
Study Completion
September 30, 2016
Last Updated
May 17, 2018
Results First Posted
May 17, 2018
Record last verified: 2018-04