Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy

NCT02003183 | Completed Results DMC

• 2 other identifiers: 11-001077IND 74944
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

CTE; TBI (Traumatic Brain Injury)

Keywords

Chronic Traumatic Encephalopathy; Traumatic Brain Injury; Cognitive Impairment; Positron Emission Tomography; [F-18]FDDNP

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline

Study Arms (1)

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).

Radiation: [F-18]FDDNP

Interventions

[F-18]FDDNP RADIATION

Each participant was injected with \[F-18\]FDDNP, a radiolabeled molecular imaging probe, prior to receiving a PET scan.

Suspected CTE

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Division of Geriatric Psychiatry, Semel Institute

Los Angeles, California, 90095, United States

Location

Related Publications (12)

• 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.

  PMID: 17143242 BACKGROUND

• Omalu 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.

  PMID: 15987548 BACKGROUND

• Guskiewicz 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.

  PMID: 17545878 BACKGROUND

• Guskiewicz 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.

  PMID: 16239884 BACKGROUND

• Omalu 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.

  PMID: 20032774 BACKGROUND

• Small 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.

  PMID: 17182990 BACKGROUND

• Small 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.

  PMID: 19124691 BACKGROUND

• Kepe 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.

  PMID: 19725833 BACKGROUND

• Small 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.

  PMID: 23343487 RESULT

• Barrio 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.

  PMID: 25848027 RESULT

• Chen 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.

  PMID: 30040711 RESULT

• Omalu 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.

  PMID: 29136240 RESULT

Biospecimen

Retention: NONE RETAINED

Samples are being stored

MeSH Terms

Conditions

Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Cognitive Dysfunction

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

Limitations and Caveats

Although the participants groups were matched for important variables, these results need interpretation with caution given the relatively small sample sizes. Differences in cerebrovascular health and other variables also could influence the results.

Results Point of Contact

• Title: Dr. Gary Small
• Organization: UCLA Semel Institute for Neuroscience and Human Behavior

gsmall@mednet.ucla.edu

3108250291

Study Officials

• Gary W Small, M.D.

  UCLA Division of Geriatric Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: December 6, 2013
• Study Start: March 1, 2013
• Primary Completion: October 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 3, 2020
• Results First Posted: November 27, 2019

Record last verified: 2020-02

Locations

US (1)