Chronic Traumatic Encephalopathy
Conditions
Brief summary
This study will explore the use of flortaucipir as a biomarker for chronic traumatic encephalopathy (CTE) and examine the relationship between clinical presentation and tau deposition.
Interventions
DRUGflorbetapir F 18
370 megabecquerel (MBq) IV single-dose
DRUGFlortaucipir F18
370 megabecquerel (MBq) IV single-dose
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
Yes
Inclusion criteria
* Male subjects consented and currently enrolled in the Diagnosing and Evaluating Traumatic Encephalopathy Using Clinical Tests (DETECT) or the Long-Term Consequences of Repetitive Brain Injury in Athletes study protocols * Can tolerate up to two PET imaging sessions * Have the ability to provide informed consent for study procedures
Exclusion criteria
* Claustrophobia * Current clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG * History of risk factors for Torsades de Pointes or are taking drugs known to cause QT-prolongation * Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer that the investigator believes would affect study participation or scan results * Have had a non-study related radiopharmaceutical imaging or treatment within 7 days prior to study PET imaging sessions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flortaucipir Visual Read as CTE Biomarker | Baseline scan | Flortaucipir uptake was rated visually by sponsor expert reader as 'No Uptake', 'Mild Uptake', 'Moderate Uptake', or 'Intense Uptake'. |
| Relationship Between Clinical Presentation and Tau Deposition (Subjects at High Risk of CTE Only) | baseline scan | The relationship between flortaucipir uptake and clinical presentation, as measured by the Mini-Mental State Examination (MMSE). Mini-mental status exam is a 30-point questionnaire that is used to measure cognitive impairment. Scores range from 0 to 30 with lower scores representing greater levels of cognitive impairment. Specified in statistical analysis plan to only be conducted in High Risk of CTE group. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between June 2014 and October 2015 from the DETECT study (National Institutes of Health grant R01NS078337) and the Arizona Alzheimer's Consortium (Long-Term Consequences of Repetitive Brain Injury in Athletes: A Longitudinal Study with Eventual Brain Donation)
Participants by arm
| Arm | Count |
|---|---|
| High Risk of CTE Subjects at high risk of developing CTE (former National Football League players) | 29 |
| Controls Former non-contact athletes | 11 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | High Risk of CTE | Controls | Total |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 8.27 | 57.4 years STANDARD_DEVIATION 6.25 | 58.2 years STANDARD_DEVIATION 7.71 |
| Amyloid status Amyloid Negative | 25 Participants | 11 Participants | 36 Participants |
| Amyloid status Amyloid positive | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 11 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| MMSE | 27.2 units on a scale STANDARD_DEVIATION 1.64 | 28.6 units on a scale STANDARD_DEVIATION 0.92 | 27.6 units on a scale STANDARD_DEVIATION 1.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 10 Participants | 24 Participants |
| Region of Enrollment United States | 29 participants | 11 participants | 40 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 29 Participants | 11 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 11 |
| other Total, other adverse events | 11 / 29 | 5 / 11 |
| serious Total, serious adverse events | 0 / 29 | 0 / 11 |
Outcome results
Primary
Flortaucipir Visual Read as CTE Biomarker
Flortaucipir uptake was rated visually by sponsor expert reader as 'No Uptake', 'Mild Uptake', 'Moderate Uptake', or 'Intense Uptake'.
Time frame: Baseline scan
Population: All subjects who received a flortaucipir scan
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Risk of CTE | Flortaucipir Visual Read as CTE Biomarker | No Uptake | 23 Participants |
| High Risk of CTE | Flortaucipir Visual Read as CTE Biomarker | Mild Uptake | 5 Participants |
| High Risk of CTE | Flortaucipir Visual Read as CTE Biomarker | Moderate Uptake | 0 Participants |
| High Risk of CTE | Flortaucipir Visual Read as CTE Biomarker | Intense Uptake | 0 Participants |
| Controls | Flortaucipir Visual Read as CTE Biomarker | Intense Uptake | 0 Participants |
| Controls | Flortaucipir Visual Read as CTE Biomarker | No Uptake | 11 Participants |
| Controls | Flortaucipir Visual Read as CTE Biomarker | Moderate Uptake | 0 Participants |
| Controls | Flortaucipir Visual Read as CTE Biomarker | Mild Uptake | 0 Participants |
Comparison: Evaluated the association between the overall brain uptake and the study groupp-value: 0.2959Fisher Exact
Primary
Relationship Between Clinical Presentation and Tau Deposition (Subjects at High Risk of CTE Only)
The relationship between flortaucipir uptake and clinical presentation, as measured by the Mini-Mental State Examination (MMSE). Mini-mental status exam is a 30-point questionnaire that is used to measure cognitive impairment. Scores range from 0 to 30 with lower scores representing greater levels of cognitive impairment. Specified in statistical analysis plan to only be conducted in High Risk of CTE group.
Time frame: baseline scan
Population: Only subjects at high risk for CTE were included in this analysis
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| High Risk of CTE | Relationship Between Clinical Presentation and Tau Deposition (Subjects at High Risk of CTE Only) | Mild Uptake | 26.800 score on a scale |
| High Risk of CTE | Relationship Between Clinical Presentation and Tau Deposition (Subjects at High Risk of CTE Only) | No Uptake | 27.348 score on a scale |
Comparison: Measured differences in clinical presentation using MMSE between subjects with no visual flortaucipir uptake, and those with mild uptake.p-value: 0.5163ANOVA