Amyloid and Tauopathy PET Imaging in Acute and Chronic Traumatic Brain Injury

NCT02266563 | Completed FDA Drug

• 1 other identifier: GCO 14-0732
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

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 conjunction with the imaging, will be able to determine whether regional brain activity is associated with specific cognitive problems. The researchers will obtain PET and neurocognitive data in 3 cohorts: subjects with a history of TBIs, subjects with mild cognitive impairment (MCI) and no TBI history, and healthy controls. The investigators aim to determine whether individuals with TBI are on the same trajectory of neurodegenerative disease seen in AD or in CTE. Because of the overlap in clinical/cognitive and some behavioral symptoms in AD and CTE, an additional biomarker tool is needed to prevent misdiagnosis. Accurate diagnosis is crucial in order to provide patients with appropriate treatment.

Conditions

Traumatic Brain Injury; Chronic Traumatic Encephalopathy; Mild Cognitive Impairment

Keywords

Traumatic Brain Injury; Chronic Traumatic Encephalopathy; Mild Cognitive Impairment; PET imaging; tauopathy; amyloid

Outcome Measures

Primary Outcomes (1)

• Uptake of [18F]T807 in the brain

  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.

  2 years

Secondary Outcomes (2)

• Uptake of [18F]AV-45 in the brain

  2 years

• Neuropsychological data composite score

  2 years

Study Arms (3)

Traumatic Brain Injury (TBI) Group

TBI subjects will have a history of one or more concussions and have a memory complaint and objective decline that is considered to be worse than others of the same age (in the absence of an acute medical event). Severity classifications of the subjects selected for past history of TBI will be based upon established criteria used in TBI research (i.e., traumatically induced physiologic disruption of brain function as indicated by at least one of the following: any period of loss of consciousness, any loss of memory for events immediately before or after the accident, any alteration in mental state at the time of the accident, focal neurologic deficits that may or may not be transient). TBI cases will be those with mTBI (single or multiple concussion). Most recent injury must have occurred at least 1 year prior to study enrollment.

Drug: Amyvid PET Scan; Drug: T807 PET scan

Mild Cognitive Impairment (MCI) Group

MCI Subjects will have MMSE scores between 24-30 (inclusive), a CDR of 0.5, have no depression, no history of TBI, and no dementia.

Drug: Amyvid PET Scan; Drug: T807 PET scan

Healthy Control Group

Healthy control subjects will have no self or informant-reported problems with cognition, no depression, no history of TBI, and no dementia.

Drug: Amyvid PET Scan; Drug: T807 PET scan

Interventions

Amyvid PET Scan DRUG

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.

Also known as: [F18] AV-45, Florbetapir, Amyvid

Healthy Control Group; Mild Cognitive Impairment (MCI) Group; Traumatic Brain Injury (TBI) Group

T807 PET scan DRUG

Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.

Also known as: [F18] AV-1451

Healthy Control Group; Mild Cognitive Impairment (MCI) Group; Traumatic Brain Injury (TBI) Group

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited through the Mount Sinai's Alzheimer's Disease Research Center (ADRC), the Memory and Aging Center (MAC), Center for Cognitive Health (CCH), and the NFL Neurological Program at the Icahn School of Medicine at Mount Sinai.

You may qualify if:

• males between 40 to 85 years of age
• individuals who participated in contact sports (e.g., active and retired NFL players, NHL players, boxers, NCAA athletes) and other individuals (including but not limited to veterans, breachers, or law enforcement officials with multiple blast exposures) who all have a history of one or more concussions and have a memory or cognitive complaint
• individuals with Mild Cognitive Impairment (MCI) and no history of concussion or TBI
• healthy controls with no history of head injury and no current cognitive or memory problems
• all participants require a study partner, who is well acquainted with the participant, to answer questions either in person or over the telephone about the individuals' activities of daily living, and to corroborate cognitive problems and past history of brain injury

You may not qualify if:

• any significant neurological disease, such as Alzheimer's disease, Parkinson's disease, vascular dementia, Huntington's disease, Pick's disease, Lewy Body Dementia, frontotemporal dementia, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, or multiple sclerosis
• any significant systemic illness or unstable medical condition, including: uncontrolled diabetes mellitus, uncorrected hypothyroidism or hyperthyroidism, or systemic cancer
• a history of schizophrenia or psychosis, alcohol or substance abuse or dependence within the past 6 months
• clinically significant impairment of liver or renal function
• significant cerebrovascular disease
• impairment of visual or auditory acuity sufficient to interfere with completion of study procedures
• education level \< 10 years
• any subjects with a history of risk factors for Torsades de Pointes, or subjects taking drugs known to prolong the QT interval
• subjects who have had 2 or more PET scans within the past year, or other significant exposure to radiation (i.e., radiation therapy)

Sponsors & Collaborators

• Samuel Gandy: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Cognitive Dysfunction; Tauopathies; Alzheimer Disease

Interventions

florbetapir; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Injury, Chronic; Neurodegenerative Diseases; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia

Study Officials

• Sam Gandy, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Dara Dickstein, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: October 17, 2014
• Study Start: January 1, 2015
• Primary Completion: December 21, 2017
• Study Completion: December 21, 2017
• Last Updated: May 2, 2019

Record last verified: 2019-04

Locations

US (1)