Clinical Trial: Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: FDDNP-PET Imaging in Persons at Risk for Chronic Traumatic Encephalopathy

Brief Summary:

The project is designed to assess early diagnosis of Chronic Traumatic Encephalopathy (CTE), a neurobehavioral syndrome manifested by failed relationships, marriages, and businesses, emotional disturbances, depression, alcohol and substance abuse, and suicide attempts and completions. CTE typically begins after a latency period of several years following single or repeated Traumatic Brain Injuries (TBIs). A history of cerebral concussion may or may not be present.

This study builds upon prior work at UCLA using Positron Emission Tomography (PET) to identify normal and abnormal functional patterns in the brain by studying persons with a history of TBI including but not limited to: amateur and professional athletes, active and veteran members of the armed forces, as well as victims of motor vehicle and work accidents, and physical battery/domestic violence.

This project aims to expand these findings to the population at large. Identification of the syndrome is critical for identifying potential individuals who are most likely to benefit from potential prevention and treatment.

Detailed Summary:

Specific Aims:

The proposed project will focus on application of small molecule radiolabeled probes of tau neurofibrillary tangles (NFTs) for in vivo positron emission tomography (PET) imaging of brain pathology for early detection and treatment monitoring of Chronic Traumatic Encephalopathy (CTE) and related neurodegenerative diseases (dementias and cognitive impairment).

Investigators plan to test the following hypothesis: PET imaging with small molecule probes, in the form of novel fluorescent dyes with radioactive labels, will demonstrate distinct cerebral patterns of binding in subjects with CTE. These cerebral patterns will differentiate from those of age-matched persons who are cognitively intact or from the patients with other neurodegenerative diseases.

The binding patterns will match the disease specific pattern of brain pathology characteristic for CTE (or other dementias, when studied). CTE distinguishes itself from other dementias by its clear tauopathy: NFTs and neuritic threads. In addition, brains of CTE subjects show white matter changes and inflammation.

In order to assess in vivo deposition of CTE's tauopathy, investigators propose to use PET imaging with [F-18]FDDNP, a molecular imaging probe for PET, with high in vitro binding affinity to NFTs and of the fibrillar tau deposits as shown with fluorescent microscopy with non-radioactive FDDNP. The analysis of [F-18]FDDNP will allow investigators to evaluate the specificity and sensitivity of this imaging probe for detection of the brain pathology and utilization of these methods for detection of early deposition and for monitoring of any therapeutic intervention aimed at stopping or reducing the deposition of neuropathologic aggregates.

FDDNP signals will be higher in those affected by CTE compared with controls in all subcortical regions and the amygdala areas that produce tau deposits following trauma.