Clinical Trial: Amyloid and Tauopathy PET Imaging in Acute and Chronic Traumatic Brain Injury

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Imaging [18F]AV-1451 and [18F]AV-45 in Acute and Chronic Traumatic Brain Injury

Brief Summary:

The potential long-term effects of Traumatic Brain Injury (TBI) are poorly understood. Repeated concussions have been associated with an elevated incidence of Alzheimer's disease (AD) along with a reduced age of onset. As repetitive TBI has been studied, a syndrome has now been identified: chronic traumatic encephalopathy (CTE). There are growing concerns about the long-term neurologic consequences of head impact exposure from routine participation in contact sports (e.g., boxing, football). Brain autopsies of athletes with confirmed CTE have demonstrated tau-immunoreactive neurofibrillary tangles and neuropil threads (known as tauopathy). The relationship between exposure to repetitive head impact and the subsequent development of chronic neurodegenerative disease has not been established. Further, as the diagnosis of CTE (defined by the presence of tauopathy) is presently made after death at autopsy, clinical tools and biomarkers for detecting it remain to be defined.

With the advent of FDA-approved PET amyloid imaging, clinicians and researchers are now able to estimate plaque density in the brains of living patients. However, there are critical limitations to amyloid imaging. Current evidence suggests that markers of the presence and severity of tauopathy may be able to address these limitations. The study will utilize both [18F] Florbetapir and [18F]-T807 PET imaging to investigate amyloid and tau accumulation in subjects with a history of concussions. In order to determine whether problems with cognition and memory are seen within the populations defined for the study, the researchers will administer a core battery of neurocognitive testing. This battery will assess cognitive abilities commonly affected by TBI, including processing speed, reaction time, new problem-solving, executive functions, attention and concentration, and learning and memory. These tests, in co

Detailed Summary:

The study involves two days of study visits. Subjects will be given a copy of the consent form on the morning of their first visit, and sign consent in a private room at Mount Sinai before any research related procedures are conducted. Subjects will then be brought to the Hess Center for Science in Medicine for injection for the [18F] AV-45 (or Amyvid) PET scan. On the second visit, which is to be conducted the day after the first visit, subjects will have the [18F]AV-1451 (or T807) PET scan and complete the neuropsychological testing battery.

Both PET scans will be done entirely for the purpose of research. The scans will be read by nuclear medicine physicians and a clinical report will be sent to the PI. Any clinically relevant findings will be sent to the treating physician and will be communicated to patients. During both visits, subjects will be allowed time for meals and breaks between study procedures.

Details of procedures:

Amyvid PET scan: At the first visit, each participant will have an Amyvid PET scan. The scan involves use of a "tracer", which is a radioactive sugar-like substance. This type of PET scan involves a tracer called AV-45 (also known as Florbetapir, and by the trade name of Amyvid). It has been approved by the FDA for use in PET imaging. It binds to beta-Amyloid plaques that may or may not be present in the brain. Amyloid plaque is a sticky substance (protein) that accumulates in the brain in larger amounts in people who may have Alzheimer's disease. A thin line will be inserted into a vein in one arm for the injection of the tracer. Subjects will begin the Amyvid PET scan 50-60 minutes after the injection of the tracer, and scanned for about 20 minutes.

T807 PET scan: On the day of the sec
Sponsor: Samuel Gandy

Current Primary Outcome: Uptake of [18F]T807 in the brain [ Time Frame: 2 years ]

To quantitatively assess the uptake of [18F]T807, a marker of tangles of tau protein in the brain, using positron emission tomography (PET) in individuals with a history of head injury or mTBI, with Mild Cognitive Impairment, and in healthy controls. Differences in uptake between the three groups will be measured.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Uptake of [18F]AV-45 in the brain [ Time Frame: 2 years ]
    To quantitatively assess the uptake of [18F]AV-45 (also known as Amyvid), a marker of Amyloid plaques, using positron emission tomography (PET) in individuals with a history of head injury or mTBI, with Mild Cognitive Impairment, and in healthy controls. Differences in uptake between the three groups will be measured.
  • Neuropsychological data composite score [ Time Frame: 2 years ]
    2. Determining the relationship between [18F]-T807 imaging and cognitive problems. Neuropsychological raw data will be standardized and converted to z-scores. Correlational analysis with imaging data will be performed.


Original Secondary Outcome: Same as current

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: October 13, 2014
Date Started: January 2015
Date Completion: December 2017
Last Updated: January 9, 2017
Last Verified: January 2017