Chronic Traumatic EncephalopathyPhase 2NCT02191267
Tau Imaging of Chronic Traumatic Encephalopathy
A Phase 2 study testing [F18]-T807, [F18]-Florbetapir and MRI/MRS in people with Chronic Traumatic Encephalopathy, run by Brigham and Women's Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 69 years, men only
- Conditions the study is for
- Chronic Traumatic Encephalopathy
- What is being tested?
- [F18]-T807, [F18]-Florbetapir and MRI/MRS
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2015to 30 Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 69 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- no history of mTBI or exposure to repetitive brain trauma
Show all 12Show fewer
- normal functioning on DETECT clinical measures
- no abnormalities on svMRI, DTI, or MRS
- 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.
Who cannot join
- 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
Show all 19Show fewer
- Control Group (comprised of 5 male participants selected from 50 control subjects in the DETECT study).
- weight > 350 lbs
- known metallic implants preventing MRI
- history of stroke or other neurological disease
- non-English speaking
- significant vision or hearing impairment
- AD Dementia Group (comprised of 5 male participants recruited from the BU Alzheimer's Disease Center (ADC) Clinical Core Registry (Dr. Stern, PI).
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston University Medical Center
Boston, Massachusetts, 02118
Brigham and Women's Hospital
Boston, Massachusetts, 02215
About this study
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.
- Conditions
- Chronic Traumatic Encephalopathy
- Being tested
- [F18]-T807, [F18]-Florbetapir, MRI/MRS, Genetic Analysis for Genetic Risk Score for Tau.
- Keywords
- CTE, Positron Emission Topography, Tau, Beta-amyloid, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Diffusion Tensor Imaging
- Medical subject headings
- Chronic Traumatic Encephalopathy, Pick Disease of the Brain, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[F18]-T807Radiation
Also called [F-18] AV-1451
[F18]-T807 PET Scan to measure tau deposition in the brain.
[F18]-FlorbetapirRadiation
Also called Amyvid
[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
MRI/MRSDevice
Also called Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Diffusion Tensor Imaging, Susceptibility Weighted Imgaging
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.
Genetic Analysis for Genetic Risk Score for Tau.Genetic
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 group | Role | What they receive |
|---|---|---|
| Presumed CTE Group | Experimental | 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. Receives: Radiation: [F18]-T807; Radiation: [F18]-Florbetapir; Device: MRI/MRS; Genetic: Genetic Analysis for Genetic Risk Score for Tau. |
| Control Group | Experimental | Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans. Receives: Radiation: [F18]-T807; Radiation: [F18]-Florbetapir; Device: MRI/MRS |
| AD Dementia Group | Experimental | Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans Receives: Radiation: [F18]-T807; Radiation: [F18]-Florbetapir; Device: MRI/MRS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tau Protein Uptake..
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.
Measured: Day 1 - of 2 day study.
Secondary outcomes (1)
Beta-Amyloid (Aβ) Protein Uptake.
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.
Measured: Day 2 - of 2 day study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startJan 2015
- Primary completion30 Sep 2016
- Study completion30 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Traumatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command, Boston University
- Responsible party
- Principal investigator, Martha E Shenton, Brigham and Women's Hospital
- Investigators
- Martha E. Shenton, Ph.D., Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02191267
- Sponsor's protocol ID
- 2014P000035
- Status last verified
- Apr 2018
- First submitted
- 15 Jul 2014
- Last updated
- 17 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.
PubMed 22683529Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.
PubMed 23234879
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tau Imaging of Chronic Traumatic Encephalopathy
- ClinicalTrials.gov ID
- NCT02191267
- Acronym / sponsor ID
- 2014P000035
- Conditions
- Chronic Traumatic Encephalopathy
- Keywords
- CTE, Positron Emission Topography, Tau, Beta-amyloid, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Diffusion Tensor Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command, Boston University
- Study start
- Jan 2015
- Primary completion
- 30 Sep 2016 (actual)
- Study completion
- 30 Sep 2016 (actual)
- First posted
- 16 Jul 2014 (estimated)
- Results
- Posted 17 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Presumed CTE Group | Experimental | Radiation: [F18]-T807, Radiation: [F18]-Florbetapir, Device: MRI/MRS, Genetic: Genetic Analysis for Genetic Risk Score for Tau.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. |
| Control Group | Experimental | Radiation: [F18]-T807, Radiation: [F18]-Florbetapir, Device: MRI/MRSInterventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans. |
| AD Dementia Group | Experimental | Radiation: [F18]-T807, Radiation: [F18]-Florbetapir, Device: MRI/MRSInterventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (19 listed)
- Control Group (comprised of 5 male participants selected from 50 control subjects in the DETECT study).
- AD Dementia Group (comprised of 5 male participants recruited from the BU Alzheimer's Disease Center (ADC) Clinical Core Registry (Dr. Stern, PI).
- history of TBI, mTBI or or exposure to repetitive brain trauma
- weight > 350 lbs
- known metallic implants preventing MRI
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 |
|---|---|---|
| [F18]-T807Also: [F-18] AV-1451[F18]-T807 PET Scan to measure tau deposition in the brain. | Radiation | AD Dementia Group, Control Group, Presumed CTE Group |
| [F18]-FlorbetapirAlso: Amyvid[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain. | Radiation | AD Dementia Group, Control Group, Presumed CTE Group |
| MRI/MRSAlso: Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Diffusion Tensor Imaging, Susceptibility Weighted ImgagingTwo 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. | Device | AD Dementia Group, Control Group, Presumed CTE Group |
| 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. | Genetic | Presumed CTE Group |
Primary outcome
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.
1 secondary outcome
Beta-Amyloid (Aβ) Protein Uptake.
Time frame: Day 2 - of 2 day study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22683529Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.
- Background: PubMed 23234879Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.
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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.
Martha E. Shenton, Ph.D. principal investigator
Brigham and Women's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing [F18]-T807, [F18]-Florbetapir and MRI/MRS in people with Chronic Traumatic Encephalopathy, run by Brigham and Women's Hospital at 2 sites 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 12 inclusion and 19 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 17 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tau Protein Uptake.. (time frame: Day 1 - of 2 day study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02191267, which also lists 2 linked publications.
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 17 May 2018.