CTENCT02003183
Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy
An observational study of CTE and TBI (Traumatic Brain Injury), run by University of California, Los Angeles at 1 site in United States.
Trial summary
This project was designed to determine brain imaging patterns using 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) with positron emission tomography (PET) in participants with suspected Chronic Traumatic Encephalopathy (CTE), a progressive degenerative… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- CTE, TBI (Traumatic Brain Injury)
- What is being tested?
- [F-18]FDDNP
- Type of treatment
- Surgery or procedure
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Dec 2018
- Phase
- Observational
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Military personnel and retired football players were exclusively men, whereas the comparative groups (AD, cognitively healthy controls) had a substantial proportion of women. Military personnel were significantly younger than the other three groups. Four of the seven military personnel were cognitively normal, and three had mild cognitive impairment. While the difference in education levels among participant groups did not reach statistical significance, pairwise comparisons indicated that military personnel had significantly lower education levels than both players and cognitively healthy individuals. Military personnel and players had significantly higher levels of depression and anxiety than did the comparison groups.
Who may be able to join
- Agreement to participate in study;
- A history of TBI resulting from, but not limited to, any of the following: contact sports, accidents, violence, or military combat;
- Age 18 or older;
- No significant cerebrovascular disease;
- Adequate visual and auditory acuity to allow neuropsychological testing;
- Screening laboratory tests without significant abnormalities that might interfere with the study.
Who cannot join
- Preexisting major neurological or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer);
- History of myocardial infarction within the previous year or unstable cardiac disease.
- Uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressure > 100),
- History of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer.
- Such current major psychiatric disorders as mania within the previous two years.
- Participants taking drugs that are known to affect [F-18]FDDNP-PET binding (e.g., ibuprofen, naproxen) were asked to stop taking medication one week prior to PET scan or excluded from the study.
- Use of any investigational drugs within the previous month, depending on drug half-life.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Division of Geriatric Psychiatry, Semel Institute
Los Angeles, California, 90095
About this study
Official title: FDDNP-PET Imaging in Persons at Risk for Chronic Traumatic Encephalopathy
This project was designed to determine brain imaging patterns using 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) with positron emission tomography (PET) in participants with suspected Chronic Traumatic Encephalopathy (CTE), a progressive degenerative disease of the brain found in people with a history of repetitive traumatic brain injuries (TBIs), characterized by personality, behavioral, and mood disturbances, cognitive impairment, and sometimes motor symptoms. Currently, CTE can only be definitely diagnosed from neuropathological examination of the brain after autopsy. Developing tools to assist in the detection of this condition in living individuals at risk would facilitate research focusing on discovering potential prevention and treatment strategies.
Read the detailed description
The project involved clinical and neuropsychological evaluations of participants with histories of TBI and symptoms suggestive of CTE; performing [F-18]FDDNP-PET scans on those participants; determining if patterns of [F-18]FDDNP binding in the brain differ from those of normal controls and Alzheimer's dementia (AD) (available from other studies). Prior research has shown that [F-18]FDDNP-PET produces binding patterns in the brain that indicate high concentrations of tau neurofibrillary tangles (NFTs) and amyloid plaques (Small et al, 2006).
The investigators aimed to test the following hypothesis: [F-18]FDDNP-PET scans will demonstrate cerebral patterns of binding in participants with suspected CTE that differ from cerebral patterns observed in cognitively-intact control participants and participants with AD. The [F-18]FDDNP-PET binding patterns are expected to be consistent with known plaque and tangle deposition patterns from previous neuropathology studies.
[F-18]FDDNP is a PET molecular imaging probe with high in vitro binding affinity to amyloid plaques, NFTs and fibrillar tau deposits as shown with fluorescent microscopy with non-radioactive FDDNP.
In addition to the above hypothesis, neuropathological data from autopsy follow-up (when it becomes available) will be used to determine correlations between regional plaque and tangle deposition patterns observed in neuropathological studies with imaging results from [F-18]FDDNP scans.
Background:
Emerging evidence indicates that repetitive, mild TBI may have long lasting effects following exposure during contact sports or military activities. As a result of recent military conflicts, a high proportion of U.S. veterans have returned from the wars in Iraq and Afghanistan with head injuries resulting from non-penetrating mechanisms.
The syndrome of CTE has been described in previous research performed on contact-sport athletes and military veterans (Omalu et al, 2005, 2006, 2010). In addition, studies of retired professional football players have demonstrated a high rate of dementia, AD, mild cognitive impairment, and depression (Guskiewicz et al, 2005, 2007).
Chronic Traumatic Encephalopathy consists of a characteristic neurobehavioral syndrome manifested by impaired personal and professional functioning, emotional disturbances, depression, alcohol and substance abuse, cognitive impairment, and suicidal behavior. It typically begins after a latency period of several years following single or repeated TBIs. A history of cerebral concussion may or may not be present. The neuroanatomical correlate consists of a tauopathy, the abnormal staining indicative of tau protein deposition in neuronal cell bodies and their axonal and dendritic connections. These representative changes of NFTs and neuritic threads are characteristic of CTE, and distinguish it from other forms of neurodegeneration.
Chronic Traumatic Encephalopathy has a classical distribution that differs than other forms of neurodegeneration (Barrio et al, 2015). The areas of involvement are the temporal and frontal cortices, in addition to the mesencephalon and upper pons, locus coeruleus, and substantia nigra. This distribution, along with the history of multiple exposures to mild TBI, the age distribution, and anatomical patterns further distinguishes this condition from AD and other forms of dementia.
Currently, the only method to diagnose CTE is through post-mortem brain examination, using special immuno-staining techniques for tau protein deposits in NFTs and neuritic threads. The ability to image tau protein collections in vivo in the form of NFTs would provide tremendous benefit for clinical management, treatment, and possibly prevention if a pre-morbid diagnosis could be confirmed. The implications for the sports communities, military organizations, and the general population, all of whom have potential exposure to TBI, are tremendous.
UCLA scientists have developed an in vivo method to measure NFTs, fibrillar tau deposits, and amyloid plaques in the brain. This discovery was led by Dr. Jorge Barrio (Department of Molecular and Medical Pharmacology), Dr. Gary Small (UCLA Division of Geriatric Psychiatry), and others. They sought a way to directly measure the physical evidence of AD - amyloid plaques and tau NFTs - in the living patient. A key to the discovery was the realization that the internal environments of these abnormal proteins were hydrophobic, that is, less friendly to water than to fat. Dr. Jorge Barrio synthesized a new group of compounds that thrived in these hydrophobic environments, and these molecules passed easily from the blood stream to brain tissues.
In initial autopsy studies, the UCLA group found that one of these new compounds (called FDDNP - UCLA Patent Ref. No. 1998-507-1) clearly displayed the well-defined characteristics needed to image these abnormal protein deposits. They then injected a radioactive form of the compound into the veins of living AD patients, and the PET scan accurately measured the concentration and location of the compound in the patient's brain. This allowed them to see for the first time, increased signals coming from living human brains in areas that contained dense collections of the abnormal proteins. .
The chemical marker essentially seeks out and temporarily attaches itself to the abnormal amyloid and tau deposits, thus providing a PET scan signal in the areas of the brain where the proteins are present in high concentrations. In healthy people without AD, these brain regions produce little or no signal. However, in people with the disease, the signal is so strong and accurate that it actually correlates with each individual's degree of memory impairment. The UCLA group has also found that people who are at risk for AD (mild cognitive impairment) have an [F-18]FDDNP signal pattern intermediate between cognitively-intact participants and those with AD, and that participants with a genetic risk for AD show higher [F-18]FDDNP binding (Small et al, 2006, 2009). Therefore, this technology could assist in early detection of the disease so that prevention treatments might be used prior to significant cognitive decline. It will also be useful in detecting and developing treatments for other conditions. Patients with dementias that have different treatment approaches (e.g., frontotemporal) have an an [F-18]FDDNP-PET pattern distinct from AD, as do patients with cognitive impairment associated with prion disease (Kepe et al, 2010).
- Conditions
- CTE, TBI (Traumatic Brain Injury)
- Being tested
- [F-18]FDDNP
- Keywords
- Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cognitive Impairment, Positron Emission Tomography, [F-18]FDDNP
- Medical subject headings
- Brain Injuries, Traumatic, Chronic Traumatic Encephalopathy, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[F-18]FDDNPRadiation
Each participant was injected with [F-18]FDDNP, a radiolabeled molecular imaging probe, prior to receiving a PET scan.
| Study group | Role | What they receive |
|---|---|---|
| Suspected CTE | A total of 22 participants with suspected CTE were studied. Each received clinical and neuropsychological assessments, [F-18]FDDNP-PET scans, and magnetic resonance imaging (MRI) scans, or computed tomography scans if they could not tolerate MRI (to assist in PET region of interest identification). Receives: Radiation: [F-18]FDDNP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distribution Volume Ratio (DVR)
The outcome measure is a ratio of the volume (in milliliters) of 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) bound within the region of interest (ROI) divided by the amount of [F-18]FDDNP in the cerebellum (reference region). Higher ratios are indicative of higher levels of tau and amyloid proteins within the ROI. The unit of measure is called the Distribution Volume Ratio (DVR).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2013 (estimated)
- Study startMar 2013
- Primary completionOct 2018
- Study completionDec 2018
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 (12)Papers the sponsor has linked to this study.
- Other trials for CTEStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gary Small, MD, University of California, Los Angeles
- Investigators
- Gary W Small, M.D., Principal investigator, UCLA Division of Geriatric Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02003183
- Sponsor's protocol ID
- 11-001077
- Other IDs
- IND 74944
- Status last verified
- Feb 2020
- First submitted
- 5 Nov 2013
- Last updated
- 3 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Omalu BI, DeKosky ST, Hamilton RL, Minster RL, Kamboh MI, Shakir AM, Wecht CH. Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery. 2006 Nov;59(5):1086-92; discussion 1092-3. doi: 10.1227/01.NEU.0000245601.69451.27.
PubMed 17143242Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery. 2005 Jul;57(1):128-34; discussion 128-34. doi: 10.1227/01.neu.0000163407.92769.ed.
PubMed 15987548Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Harding HP Jr, Matthews A, Mihalik JR, Cantu RC. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007 Jun;39(6):903-9. doi: 10.1249/mss.0b013e3180383da5.
PubMed 17545878Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, Jordan BD. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 Oct;57(4):719-26; discussion 719-26. doi: 10.1093/neurosurgery/57.4.719.
PubMed 16239884Omalu BI, Bailes J, Hammers JL, Fitzsimmons RP. Chronic traumatic encephalopathy, suicides and parasuicides in professional American athletes: the role of the forensic pathologist. Am J Forensic Med Pathol. 2010 Jun;31(2):130-2. doi: 10.1097/PAF.0b013e3181ca7f35.
PubMed 20032774Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63. doi: 10.1056/NEJMoa054625.
PubMed 17182990Small GW, Siddarth P, Burggren AC, Kepe V, Ercoli LM, Miller KJ, Lavretsky H, Thompson PM, Cole GM, Huang SC, Phelps ME, Bookheimer SY, Barrio JR. Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementia. Arch Gen Psychiatry. 2009 Jan;66(1):81-7. doi: 10.1001/archgenpsychiatry.2008.516.
PubMed 19124691Kepe V, Ghetti B, Farlow MR, Bresjanac M, Miller K, Huang SC, Wong KP, Murrell JR, Piccardo P, Epperson F, Repovs G, Smid LM, Petric A, Siddarth P, Liu J, Satyamurthy N, Small GW, Barrio JR. PET of brain prion protein amyloid in Gerstmann-Straussler-Scheinker disease. Brain Pathol. 2010 Mar;20(2):419-30. doi: 10.1111/j.1750-3639.2009.00306.x. Epub 2009 Jun 9.
PubMed 19725833Small GW, Kepe V, Siddarth P, Ercoli LM, Merrill DA, Donoghue N, Bookheimer SY, Martinez J, Omalu B, Bailes J, Barrio JR. PET scanning of brain tau in retired national football league players: preliminary findings. Am J Geriatr Psychiatry. 2013 Feb;21(2):138-44. doi: 10.1016/j.jagp.2012.11.019. Epub 2013 Jan 22.
PubMed 23343487Barrio JR, Small GW, Wong KP, Huang SC, Liu J, Merrill DA, Giza CC, Fitzsimmons RP, Omalu B, Bailes J, Kepe V. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging. Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):E2039-47. doi: 10.1073/pnas.1409952112. Epub 2015 Apr 6.
PubMed 25848027Chen ST, Siddarth P, Merrill DA, Martinez J, Emerson ND, Liu J, Wong KP, Satyamurthy N, Giza CC, Huang SC, Fitzsimmons RP, Bailes J, Omalu B, Barrio JR, Small GW. FDDNP-PET Tau Brain Protein Binding Patterns in Military Personnel with Suspected Chronic Traumatic Encephalopathy1. J Alzheimers Dis. 2018;65(1):79-88. doi: 10.3233/JAD-171152.
PubMed 30040711Omalu B, Small GW, Bailes J, Ercoli LM, Merrill DA, Wong KP, Huang SC, Satyamurthy N, Hammers JL, Lee J, Fitzsimmons RP, Barrio JR. Postmortem Autopsy-Confirmation of Antemortem [F-18]FDDNP-PET Scans in a Football Player With Chronic Traumatic Encephalopathy. Neurosurgery. 2018 Feb 1;82(2):237-246. doi: 10.1093/neuros/nyx536.
PubMed 29136240
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FDDNP-PET Imaging in Persons at Risk for Chronic Traumatic Encephalopathy
- ClinicalTrials.gov ID
- NCT02003183
- Acronym / sponsor ID
- 11-001077
- Conditions
- CTE, TBI (Traumatic Brain Injury)
- Keywords
- Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cognitive Impairment, Positron Emission Tomography, [F-18]FDDNP
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Mar 2013 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 6 Dec 2013 (estimated)
- Results
- Posted 27 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project was designed to determine brain imaging patterns using 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) with positron emission tomography (PET) in participants with suspected Chronic Traumatic Encephalopathy (CTE), a progressive degenerative disease of the brain found in people with a history of repetitive traumatic brain injuries (TBIs), characterized by personality, behavioral, and mood disturbances, cognitive impairment, and sometimes motor symptoms. Currently, CTE can only be definitely diagnosed from neuropathological examination of the brain after autopsy. Developing tools to assist in the detection of this condition in living individuals at risk would facilitate research focusing on discovering potential prevention and treatment strategies.
Detailed description
The project involved clinical and neuropsychological evaluations of participants with histories of TBI and symptoms suggestive of CTE; performing [F-18]FDDNP-PET scans on those participants; determining if patterns of [F-18]FDDNP binding in the brain differ from those of normal controls and Alzheimer's dementia (AD) (available from other studies). Prior research has shown that [F-18]FDDNP-PET produces binding patterns in the brain that indicate high concentrations of tau neurofibrillary tangles (NFTs) and amyloid plaques (Small et al, 2006).
The investigators aimed to test the following hypothesis: [F-18]FDDNP-PET scans will demonstrate cerebral patterns of binding in participants with suspected CTE that differ from cerebral patterns observed in cognitively-intact control participants and participants with AD. The [F-18]FDDNP-PET binding patterns are expected to be consistent with known plaque and tangle deposition patterns from previous neuropathology studies.
[F-18]FDDNP is a PET molecular imaging probe with high in vitro binding affinity to amyloid plaques, NFTs and fibrillar tau deposits as shown with fluorescent microscopy with non-radioactive FDDNP.
In addition to the above hypothesis, neuropathological data from autopsy follow-up (when it becomes available) will be used to determine correlations between regional plaque and tangle deposition patterns observed in neuropathological studies with imaging results from [F-18]FDDNP scans.
Background:
Emerging evidence indicates that repetitive, mild TBI may have long lasting effects following exposure during contact sports or military activities. As a result of recent military conflicts, a high proportion of U.S. veterans have returned from the wars in Iraq and Afghanistan with head injuries resulting from non-penetrating mechanisms.
The syndrome of CTE has been described in previous research performed on contact-sport athletes and military veterans (Omalu et al, 2005, 2006, 2010). In addition, studies of retired professional football players have demonstrated a high rate of dementia, AD, mild cognitive impairment, and depression (Guskiewicz et al, 2005, 2007).
Chronic Traumatic Encephalopathy consists of a characteristic neurobehavioral syndrome manifested by impaired personal and professional functioning, emotional disturbances, depression, alcohol and substance abuse, cognitive impairment, and suicidal behavior. It typically begins after a latency period of several years following single or repeated TBIs. A history of cerebral concussion may or may not be present. The neuroanatomical correlate consists of a tauopathy, the abnormal staining indicative of tau protein deposition in neuronal cell bodies and their axonal and dendritic connections. These representative changes of NFTs and neuritic threads are characteristic of CTE, and distinguish it from other forms of neurodegeneration.
Chronic Traumatic Encephalopathy has a classical distribution that differs than other forms of neurodegeneration (Barrio et al, 2015). The areas of involvement are the temporal and frontal cortices, in addition to the mesencephalon and upper pons, locus coeruleus, and substantia nigra. This distribution, along with the history of multiple exposures to mild TBI, the age distribution, and anatomical patterns further distinguishes this condition from AD and other forms of dementia.
Currently, the only method to diagnose CTE is through post-mortem brain examination, using special immuno-staining techniques for tau protein deposits in NFTs and neuritic threads. The ability to image tau protein collections in vivo in the form of NFTs would provide tremendous benefit for clinical management, treatment, and possibly prevention if a pre-morbid diagnosis could be confirmed. The implications for the sports communities, military organizations, and the general population, all of whom have potential exposure to TBI, are tremendous.
UCLA scientists have developed an in vivo method to measure NFTs, fibrillar tau deposits, and amyloid plaques in the brain. This discovery was led by Dr. Jorge Barrio (Department of Molecular and Medical Pharmacology), Dr. Gary Small (UCLA Division of Geriatric Psychiatry), and others. They sought a way to directly measure the physical evidence of AD - amyloid plaques and tau NFTs - in the living patient. A key to the discovery was the realization that the internal environments of these abnormal proteins were hydrophobic, that is, less friendly to water than to fat. Dr. Jorge Barrio synthesized a new group of compounds that thrived in these hydrophobic environments, and these molecules passed easily from the blood stream to brain tissues.
In initial autopsy studies, the UCLA group found that one of these new compounds (called FDDNP - UCLA Patent Ref. No. 1998-507-1) clearly displayed the well-defined characteristics needed to image these abnormal protein deposits. They then injected a radioactive form of the compound into the veins of living AD patients, and the PET scan accurately measured the concentration and location of the compound in the patient's brain. This allowed them to see for the first time, increased signals coming from living human brains in areas that contained dense collections of the abnormal proteins. .
The chemical marker essentially seeks out and temporarily attaches itself to the abnormal amyloid and tau deposits, thus providing a PET scan signal in the areas of the brain where the proteins are present in high concentrations. In healthy people without AD, these brain regions produce little or no signal. However, in people with the disease, the signal is so strong and accurate that it actually correlates with each individual's degree of memory impairment. The UCLA group has also found that people who are at risk for AD (mild cognitive impairment) have an [F-18]FDDNP signal pattern intermediate between cognitively-intact participants and those with AD, and that participants with a genetic risk for AD show higher [F-18]FDDNP binding (Small et al, 2006, 2009). Therefore, this technology could assist in early detection of the disease so that prevention treatments might be used prior to significant cognitive decline. It will also be useful in detecting and developing treatments for other conditions. Patients with dementias that have different treatment approaches (e.g., frontotemporal) have an an [F-18]FDDNP-PET pattern distinct from AD, as do patients with cognitive impairment associated with prion disease (Kepe et al, 2010).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Suspected CTE | – | Radiation: [F-18]FDDNPA total of 22 participants with suspected CTE were studied. Each received clinical and neuropsychological assessments, [F-18]FDDNP-PET scans, and magnetic resonance imaging (MRI) scans, or computed tomography scans if they could not tolerate MRI (to assist in PET region of interest identification). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Military personnel and retired football players were exclusively men, whereas the comparative groups (AD, cognitively healthy controls) had a substantial proportion of women. Military personnel were significantly younger than the other three groups. Four of the seven military personnel were cognitively normal, and three had mild cognitive impairment. While the difference in education levels among participant groups did not reach statistical significance, pairwise comparisons indicated that military personnel had significantly lower education levels than both players and cognitively healthy individuals. Military personnel and players had significantly higher levels of depression and anxiety than did the comparison groups.
Key inclusion criteria (6 listed)
- Agreement to participate in study;
- A history of TBI resulting from, but not limited to, any of the following: contact sports, accidents, violence, or military combat;
- Age 18 or older;
- No significant cerebrovascular disease;
- Adequate visual and auditory acuity to allow neuropsychological testing;
Key exclusion criteria (7 listed)
- Preexisting major neurological or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer);
- History of myocardial infarction within the previous year or unstable cardiac disease.
- Uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressure > 100),
- History of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer.
- Such current major psychiatric disorders as mania within the previous two years.
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 |
|---|---|---|
| [F-18]FDDNPEach participant was injected with [F-18]FDDNP, a radiolabeled molecular imaging probe, prior to receiving a PET scan. | Radiation | Suspected CTE |
Primary outcome
Distribution Volume Ratio (DVR)
Time frame: Baseline
The outcome measure is a ratio of the volume (in milliliters) of 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) bound within the region of interest (ROI) divided by the amount of [F-18]FDDNP in the cerebellum (reference region). Higher ratios are indicative of higher levels of tau and amyloid proteins within the ROI. The unit of measure is called the Distribution Volume Ratio (DVR).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17143242Omalu BI, DeKosky ST, Hamilton RL, Minster RL, Kamboh MI, Shakir AM, Wecht CH. Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery. 2006 Nov;59(5):1086-92; discussion 1092-3. doi: 10.1227/01.NEU.0000245601.69451.27.
- Background: PubMed 15987548Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery. 2005 Jul;57(1):128-34; discussion 128-34. doi: 10.1227/01.neu.0000163407.92769.ed.
- Background: PubMed 17545878Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Harding HP Jr, Matthews A, Mihalik JR, Cantu RC. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007 Jun;39(6):903-9. doi: 10.1249/mss.0b013e3180383da5.
- Background: PubMed 16239884Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, Jordan BD. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 Oct;57(4):719-26; discussion 719-26. doi: 10.1093/neurosurgery/57.4.719.
- Background: PubMed 20032774Omalu BI, Bailes J, Hammers JL, Fitzsimmons RP. Chronic traumatic encephalopathy, suicides and parasuicides in professional American athletes: the role of the forensic pathologist. Am J Forensic Med Pathol. 2010 Jun;31(2):130-2. doi: 10.1097/PAF.0b013e3181ca7f35.
- Background: PubMed 17182990Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63. doi: 10.1056/NEJMoa054625.
- Background: PubMed 19124691Small GW, Siddarth P, Burggren AC, Kepe V, Ercoli LM, Miller KJ, Lavretsky H, Thompson PM, Cole GM, Huang SC, Phelps ME, Bookheimer SY, Barrio JR. Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementia. Arch Gen Psychiatry. 2009 Jan;66(1):81-7. doi: 10.1001/archgenpsychiatry.2008.516.
- Background: PubMed 19725833Kepe V, Ghetti B, Farlow MR, Bresjanac M, Miller K, Huang SC, Wong KP, Murrell JR, Piccardo P, Epperson F, Repovs G, Smid LM, Petric A, Siddarth P, Liu J, Satyamurthy N, Small GW, Barrio JR. PET of brain prion protein amyloid in Gerstmann-Straussler-Scheinker disease. Brain Pathol. 2010 Mar;20(2):419-30. doi: 10.1111/j.1750-3639.2009.00306.x. Epub 2009 Jun 9.
- Results publication: PubMed 23343487Small GW, Kepe V, Siddarth P, Ercoli LM, Merrill DA, Donoghue N, Bookheimer SY, Martinez J, Omalu B, Bailes J, Barrio JR. PET scanning of brain tau in retired national football league players: preliminary findings. Am J Geriatr Psychiatry. 2013 Feb;21(2):138-44. doi: 10.1016/j.jagp.2012.11.019. Epub 2013 Jan 22.
- Results publication: PubMed 25848027Barrio JR, Small GW, Wong KP, Huang SC, Liu J, Merrill DA, Giza CC, Fitzsimmons RP, Omalu B, Bailes J, Kepe V. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging. Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):E2039-47. doi: 10.1073/pnas.1409952112. Epub 2015 Apr 6.
- Results publication: PubMed 30040711Chen ST, Siddarth P, Merrill DA, Martinez J, Emerson ND, Liu J, Wong KP, Satyamurthy N, Giza CC, Huang SC, Fitzsimmons RP, Bailes J, Omalu B, Barrio JR, Small GW. FDDNP-PET Tau Brain Protein Binding Patterns in Military Personnel with Suspected Chronic Traumatic Encephalopathy1. J Alzheimers Dis. 2018;65(1):79-88. doi: 10.3233/JAD-171152.
- Results publication: PubMed 29136240Omalu B, Small GW, Bailes J, Ercoli LM, Merrill DA, Wong KP, Huang SC, Satyamurthy N, Hammers JL, Lee J, Fitzsimmons RP, Barrio JR. Postmortem Autopsy-Confirmation of Antemortem [F-18]FDDNP-PET Scans in a Football Player With Chronic Traumatic Encephalopathy. Neurosurgery. 2018 Feb 1;82(2):237-246. doi: 10.1093/neuros/nyx536.
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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.
Gary W Small, M.D. principal investigator
UCLA Division of Geriatric Psychiatry
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 CTE and TBI (Traumatic Brain Injury), run by University of California, Los Angeles 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 6 inclusion and 7 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 3 Mar 2020. 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?
Yes. Results are posted in the registry (first posted 27 Nov 2019). 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?
Distribution Volume Ratio (DVR) (time frame: Baseline). 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 NCT02003183, which also lists 12 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 3 Mar 2020.