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Tau Imaging of Chronic Traumatic Encephalopathy

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ClinicalTrials.gov Identifier: NCT02191267
Recruitment Status : Completed
First Posted : July 16, 2014
Results First Posted : May 17, 2018
Last Update Posted : May 17, 2018
Sponsor:
Collaborators:
U.S. Army Medical Research and Development Command
Boston University
Information provided by (Responsible Party):
Martha E Shenton, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE July 15, 2014
First Posted Date  ICMJE July 16, 2014
Results First Submitted Date  ICMJE March 15, 2018
Results First Posted Date  ICMJE May 17, 2018
Last Update Posted Date May 17, 2018
Study Start Date  ICMJE January 2015
Actual Primary Completion Date September 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
Tau Protein Uptake.. [ Time Frame: Up to 3 years ]
Evidence of differences in tau protein uptake as measured by the [18F]-T807 PET ligand will be assessed in our 3 subject groups.
Change History Complete list of historical versions of study NCT02191267 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
Beta-Amyloid (Aβ) Protein Uptake. [ Time Frame: Up to 3 years. ]
Evidence of differences in Aβ protein uptake as measured by the [18F]-florbetapir PET ligand will be assessed in our 3 subject groups.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 15, 2014)
  • MR Biomarkers of Chronic Traumatic Encephalopathy (CTE). [ Time Frame: Up to 3 years. ]
    MR (Magnetic Resonance) biomarkers for CTE derived from svMRI, DTI and MRS that are associated with brain tau findings measured by PET and previously acquired CSF p-tau levels will be developed.
  • Genetic Risk Score for Tau. [ Time Frame: Up to 3 years. ]
    We will compare tau load (measured by PET tau ligand uptake and CSF p-tau level) with a measure of genetic susceptibility to tau load, referred to as the genetic risk score for tau.
 
Descriptive Information
Brief Title  ICMJE Tau Imaging of Chronic Traumatic Encephalopathy
Official Title  ICMJE Tau Imaging of Chronic Traumatic Encephalopathy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Chronic Traumatic Encephalopathy
Intervention  ICMJE
  • Radiation: [F18]-T807
    [F18]-T807 PET Scan to measure tau deposition in the brain.
    Other Name: [F-18] AV-1451
  • Radiation: [F18]-Florbetapir
    [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
    Other Name: Amyvid
  • Device: MRI/MRS
    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:
    • Magnetic Resonance Imaging
    • Magnetic Resonance Spectroscopy
    • Diffusion Tensor Imaging
    • Susceptibility Weighted Imgaging
    • One-dimensional Spectroscopy
    • Two-dimensional Spectroscopy
  • Genetic: Genetic Analysis for Genetic Risk Score for Tau.
    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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Radiation: [F18]-T807
    • Radiation: [F18]-Florbetapir
    • Device: MRI/MRS
    • Genetic: Genetic Analysis for Genetic Risk Score for Tau.
  • Experimental: Control Group
    Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans.
    Interventions:
    • Radiation: [F18]-T807
    • Radiation: [F18]-Florbetapir
    • Device: MRI/MRS
  • Experimental: AD Dementia Group
    Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans
    Interventions:
    • Radiation: [F18]-T807
    • Radiation: [F18]-Florbetapir
    • Device: MRI/MRS
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 15, 2014)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 30, 2016
Actual Primary Completion Date September 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  1. 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
  2. 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
  3. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 40 Years to 69 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02191267
Other Study ID Numbers  ICMJE 2014P000035
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Martha E Shenton, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE
  • U.S. Army Medical Research and Development Command
  • Boston University
Investigators  ICMJE
Principal Investigator: Martha E. Shenton, Ph.D. Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP