Alzheimer's Disease
Conditions
Brief summary
Subjects enrolled in the Professional Fighters Brain Health Study (PFBHS) will receive flortaucipir to explore its use as a biomarker for brain injury related to repetitive head trauma and to examine the relationship between clinical presentation and tau deposition.
Interventions
DRUGFlortaucipir F18
IV injection, 370 megabecquerel (MBq) (10 mCi)
PROCEDUREBrain PET scan
positron emission tomography (PET) scan of the brain 75-105 minutes post injection
Sponsors
The Cleveland Clinic
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All Subjects * Currently enrolled in the PFBHS protocol and have participated in a minimum of 10 professional fights * Can tolerate Positron Emission Tomography (PET) scan procedures * Have the ability to provide informed consent Subjects with cognitive impairment * Have subjective cognitive complaints or objective decline or impairment as determined by the investigator
Exclusion criteria
* Have behavior dysfunction that is likely to interfere with imaging * Are claustrophobic or otherwise unable to tolerate the imaging procedure * Have current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram * A history of additional risk factors for Torsades de Pointes (TdP) or are taking drugs that are known to cause QT-prolongation * Have a current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer * Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session * Have current drug or alcohol dependence or alcohol dependence within the past 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flortaucipir Imaging (Quantitative) Between Cognitive Groups | baseline scan | Standard Uptake Value Ratio (SUVr) by subject enrollment group (cognitive impaired/normal) across weighted cortical average, frontal, temporal, parietal, and occipital brain regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. |
| Flortaucipir Imaging (Quantitative) Between Fighter Groups | baseline scan | Standard Uptake Value Ratio (SUVr) by subject enrollment group (active fighter/retired fighter) across weighted cortical average, frontal, temporal, parietal, and occipital brain regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. |
| Flortaucipir Imaging (Qualitative) Between Cognitive Groups | baseline scan | Qualitative read results (no, mild, moderate, or intense uptake) compared between cognitively impaired (CI) and cognitively normal (CN) groups. |
| Flortaucipir Imaging (Qualitative) Between Fighter Groups | baseline scan | Qualitative read results (no, mild, moderate, or intense uptake) compared between active and retired fighter groups |
Countries
United States
Participant flow
Recruitment details
Enrollment occurred between Feb 2015 and Feb 2017
Pre-assignment details
Five subjects enrolled in the study but did not receive a flortaucipir PET scan (2 active, 3 retired). Two additional subjects in the active fighters group did not have the minimum 10 fights required for inclusion into the study, and therefore were considered not to have completed the study. However, their PET scan results were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Active Professional Fighters Active professional fighters (with and without cognitive impairment) receiving a flortaucipir PET scan | 10 |
| Retired Professional Fighters Retired professional fighters (with and without cognitive impairment) receiving a flortaucipir PET scan | 20 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | <10 professional fights | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Retired Professional Fighters | Total | Active Professional Fighters |
|---|---|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 10.21 | 42.3 years STANDARD_DEVIATION 11.49 | 31.7 years STANDARD_DEVIATION 4.27 |
| Amyloid status Amyloid negative | 14 Participants | 15 Participants | 1 Participants |
| Amyloid status Amyloid positive | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 10 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 20 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 12 Participants | 5 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 16 Participants | 3 Participants |
| Region of Enrollment United States | 20 participants | 30 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 30 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 20 |
| other Total, other adverse events | 0 / 10 | 2 / 20 |
| serious Total, serious adverse events | 0 / 10 | 0 / 20 |
Outcome results
Primary
Flortaucipir Imaging (Qualitative) Between Cognitive Groups
Qualitative read results (no, mild, moderate, or intense uptake) compared between cognitively impaired (CI) and cognitively normal (CN) groups.
Time frame: baseline scan
Population: Cognitively impaired fighters either had subjective cognitive complaints or objective decline or impairment as determined by the investigator.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | No Uptake | 16 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Mild Uptake | 2 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Intense Uptake | 0 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Moderate Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Intense Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | No Uptake | 12 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Mild Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Cognitive Groups | Moderate Uptake | 0 Participants |
Primary
Flortaucipir Imaging (Qualitative) Between Fighter Groups
Qualitative read results (no, mild, moderate, or intense uptake) compared between active and retired fighter groups
Time frame: baseline scan
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | No Uptake | 10 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Mild Uptake | 0 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Moderate Uptake | 0 Participants |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Intense Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Intense Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | No Uptake | 18 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Moderate Uptake | 0 Participants |
| Cognitively Normal Fighters | Flortaucipir Imaging (Qualitative) Between Fighter Groups | Mild Uptake | 2 Participants |
Primary
Flortaucipir Imaging (Quantitative) Between Cognitive Groups
Standard Uptake Value Ratio (SUVr) by subject enrollment group (cognitive impaired/normal) across weighted cortical average, frontal, temporal, parietal, and occipital brain regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline scan
Population: Cognitively impaired fighters either had subjective cognitive complaints or objective decline or impairment as determined by the investigator.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Occipital | 0.9513 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Weighted cortical average | 1.0048 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Frontal | 0.9731 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Temporal | 0.9867 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Parietal | 0.9472 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Parietal | 0.9288 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Temporal | 0.9305 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Weighted cortical average | 0.971 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Occipital | 0.9247 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Cognitive Groups | Frontal | 0.9357 standardized uptake value ratio (SUVr) |
Primary
Flortaucipir Imaging (Quantitative) Between Fighter Groups
Standard Uptake Value Ratio (SUVr) by subject enrollment group (active fighter/retired fighter) across weighted cortical average, frontal, temporal, parietal, and occipital brain regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline scan
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Temporal | 0.9838 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Parietal | 0.9623 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Frontal | 0.9816 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Occipital | 0.9632 standardized uptake value ratio (SUVr) |
| Cognitively Impaired Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Weighted cortical average | 0.9965 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Occipital | 0.9127 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Weighted cortical average | 0.9794 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Frontal | 0.9273 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Parietal | 0.9137 standardized uptake value ratio (SUVr) |
| Cognitively Normal Fighters | Flortaucipir Imaging (Quantitative) Between Fighter Groups | Temporal | 0.9334 standardized uptake value ratio (SUVr) |