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Tau Imaging of Chronic Traumatic Encephalopathy

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02191267
First Posted: July 16, 2014
Last Update Posted: February 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
U.S. Army Medical Research and Materiel Command
Boston University
Information provided by (Responsible Party):
Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital
  Purpose

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.


Condition Intervention Phase
Chronic Traumatic Encephalopathy Radiation: [F18]-T807 Radiation: [F18]-Florbetapir Device: MRI/MRS Genetic: Genetic Analysis for Genetic Risk Score for Tau. Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Tau Imaging of Chronic Traumatic Encephalopathy

Resource links provided by NLM:


Further study details as provided by Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 30
Study Start Date: January 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Experimental: Control Group
Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans.
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
Experimental: AD Dementia Group
Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02191267


Locations
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Marcelo F. Di Carli, MD, FACC
U.S. Army Medical Research and Materiel Command
Boston University
Investigators
Principal Investigator: Martha E. Shenton, Ph.D. Brigham and Women's Hospital
  More Information

Publications:
Responsible Party: Marcelo F. Di Carli, MD, FACC, Chief, Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02191267     History of Changes
Other Study ID Numbers: 2014P000035
First Submitted: July 15, 2014
First Posted: July 16, 2014
Last Update Posted: February 3, 2017
Last Verified: February 2017

Keywords provided by Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital:
CTE
Positron Emission Topography
Tau
Beta-amyloid
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Diffusion Tensor Imaging

Additional relevant MeSH terms:
Brain Diseases
Brain Injuries
Dementia
Brain Injury, Chronic
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Neurocognitive Disorders
Mental Disorders
Brain Damage, Chronic


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