Traumatic Brain InjuryNCT02266563
Amyloid and Tauopathy PET Imaging in Acute and Chronic Traumatic Brain Injury
An observational study of Traumatic Brain Injury and Chronic Traumatic Encephalopathy, run by Samuel Gandy at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury, Chronic Traumatic Encephalopathy, Mild Cognitive Impairment
- What is being tested?
- Amyvid PET Scan and T807 PET scan
- Type of treatment
- Injection or infusion
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 21 Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Imaging [18F]AV-1451 and [18F]AV-45 in Acute and Chronic Traumatic Brain Injury
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.
Read the detailed description
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 second visit, each participant will have an [F18] AV-1451 PET scan, also known as a T807 PET scan. This type of PET scan is being studied by the FDA as a diagnostic tool. This PET scan involves a very similar procedure to the Amyvid PET scan the day before. Like the Amyvid scan, a thin line will be inserted into a vein in one arm for the injection of the AV-1451 radiotracer. This tracer binds to clusters of Tau protein inside the brain called neurofibrillary tangles. These tangles are associated with both Alzheimer's disease and memory problems that may be related to multiple head injuries or concussions. Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.
Neuropsychological testing battery: The neuropsychological assessment is a battery of pencil and paper tests that measure memory and thinking abilities. In total it takes about two hours to complete.
- Being tested
- Amyvid PET Scan, T807 PET scan
- Keywords
- Traumatic Brain Injury, Chronic Traumatic Encephalopathy, Mild Cognitive Impairment, PET imaging, tauopathy, amyloid
- Medical subject headings
- Brain Injuries, Traumatic, Chronic Traumatic Encephalopathy, Cognitive Dysfunction, Tauopathies, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amyvid PET ScanDrug
Also called [F18] AV-45, Florbetapir, Amyvid
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 scanDrug
Also called [F18] AV-1451
Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Amyvid PET Scan; Drug: T807 PET scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (2)
Uptake of [18F]AV-45 in the brain
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.
Measured: 2 years
Neuropsychological data composite score
- 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2014 (estimated)
- Study startJan 2015
- Primary completion21 Dec 2017
- Study completion21 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Gandy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Samuel Gandy, Icahn School of Medicine at Mount Sinai
- Investigators
- Sam Gandy, MD, PhD, Principal investigator, Icahn School of Medicine at Mount SinaiDara Dickstein, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02266563
- Sponsor's protocol ID
- GCO 14-0732
- Status last verified
- Apr 2019
- First submitted
- 13 Oct 2014
- Last updated
- 2 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging [18F]AV-1451 and [18F]AV-45 in Acute and Chronic Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02266563
- Acronym / sponsor ID
- GCO 14-0732
- Keywords
- Traumatic Brain Injury, Chronic Traumatic Encephalopathy, Mild Cognitive Impairment, PET imaging, tauopathy, amyloid
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Samuel GandyUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- 21 Dec 2017 (actual)
- Study completion
- 21 Dec 2017 (actual)
- First posted
- 17 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 second visit, each participant will have an [F18] AV-1451 PET scan, also known as a T807 PET scan. This type of PET scan is being studied by the FDA as a diagnostic tool. This PET scan involves a very similar procedure to the Amyvid PET scan the day before. Like the Amyvid scan, a thin line will be inserted into a vein in one arm for the injection of the AV-1451 radiotracer. This tracer binds to clusters of Tau protein inside the brain called neurofibrillary tangles. These tangles are associated with both Alzheimer's disease and memory problems that may be related to multiple head injuries or concussions. Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes.
Neuropsychological testing battery: The neuropsychological assessment is a battery of pencil and paper tests that measure memory and thinking abilities. In total it takes about two hours to complete.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Traumatic Brain Injury (TBI) Group | – | Drug: Amyvid PET Scan, Drug: T807 PET scanTBI 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. |
| Mild Cognitive Impairment (MCI) Group | – | Drug: Amyvid PET Scan, Drug: T807 PET scanMCI Subjects will have MMSE scores between 24-30 (inclusive), a CDR of 0.5, have no depression, no history of TBI, and no dementia. |
| Healthy Control Group | – | Drug: Amyvid PET Scan, Drug: T807 PET scanHealthy control subjects will have no self or informant-reported problems with cognition, no depression, no history of TBI, and no dementia. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amyvid PET ScanAlso: [F18] AV-45, Florbetapir, AmyvidA 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. | Drug | Healthy Control Group, Mild Cognitive Impairment (MCI) Group, Traumatic Brain Injury (TBI) Group |
| T807 PET scanAlso: [F18] AV-1451Scanning will begin 80 minutes after the injection of the tracer, and last for about 20 minutes. | Drug | Healthy Control Group, Mild Cognitive Impairment (MCI) Group, Traumatic Brain Injury (TBI) Group |
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.
2 secondary outcomes
Uptake of [18F]AV-45 in the brain
Time frame: 2 years
Neuropsychological data composite score
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam Gandy, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
Dara Dickstein, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury and Chronic Traumatic Encephalopathy, run by Samuel Gandy at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uptake of [18F]T807 in the brain (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2019.