Corticobasal Degeneration, Progressive Supranuclear Palsy
Conditions
Brief summary
This study will evaluate flortaucipir for brain imaging of tau in subjects with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and healthy volunteers.
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
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Cognitively Healthy Volunteers * Mini-mental state examination (MMSE) ≥ 28 * No history of cognitive decline or parkinsonian motor disorder CBD and PSP subjects * Able to walk 10 steps with minimal assistance * MMSE ≥ 14 and ≤ 30 * Subject has a reliable study partner who agrees to accompany subject to visits and spends at least 5 hours per week with the subject PSP subjects only * Meet National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria as modified for the Neuroprotection and Natural History Parkinson Plus Syndromes (NNIPPS) clinical trial CBD subjects only * Meets 2013 consensus criteria for possible or probable corticobasal degeneration, corticobasal syndrome (CBS) subtype
Exclusion criteria
All subjects * Have evidence of structural abnormalities such as vascular disease, large strokes or severe white matter disease or other mass lesion on screening MRI * Claustrophobia * Current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (e.g. corrected QT interval \>450 msec) * Have a history of risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of long QT syndrome) * Have a current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer * Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception * Have received or participated in a trial with investigational medications in the past 30 days * Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session * Have a history of neuroleptic use for a prolonged period of time or within the past 6 months PSP and CBD subjects * Have evidence of amyloid deposition * Meet National Institute on Aging-Alzheimer's Association criteria for probable Alzheimer's Disease * Have any other neurological condition other than CBS or PSP that could account for cognitive or motor deficits * Serum or plasma progranulin level less than one standard deviation below the normal subject mean for the laboratory performing the assay * Have a high-risk family history suggestive of tar DNA binding protein (TDP)-43 pathology or known mutations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | baseline and 9 month scans | A PSP/CBD (PSP = progressive supranuclear palsy; CBD = corticobasal degeneration) targeted composite Standardized Uptake Value ratio (SUVr) was calculated as the voxel-weighted average from the regional SUVr values of the left, right, and total globus pallidus and the dentate nuclei of the cerebellum for both the baseline and 9 month PET scans. Additionally, a global cortical Alzheimer's Disease (AD)-targeted cortical SUVr was calculated. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited between Aug 2014 and Jul 2016.
Participants by arm
| Arm | Count |
|---|---|
| PSP Subjects Amyloid negative subjects with PSP receiving a flortaucipir PET scan at baseline and at 9 months.
Flortaucipir F18 PET scan: IV injection, 370 MBq (10 mCi) | 20 |
| CBD Subjects Amyloid negative subjects with CBD receiving a flortaucipir PET scan at baseline and at 9 months.
Flortaucipir F18 PET scan: IV injection, 370 MBq (10 mCi) | 6 |
| Healthy Volunteers Healthy volunteers receiving a flortaucipir PET scan at baseline.
Flortaucipir F18 PET scan: IV injection, 370 MBq (10 mCi) | 3 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | PSP Subjects | CBD Subjects | Healthy Volunteers | Total |
|---|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 5.88 | 72.2 years STANDARD_DEVIATION 7.41 | 68.7 years STANDARD_DEVIATION 10.41 | 69.8 years STANDARD_DEVIATION 6.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 6 Participants | 3 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mini Mental Status Exam (MMSE) | 26.5 units on a scale STANDARD_DEVIATION 3.12 | 26.3 units on a scale STANDARD_DEVIATION 4.32 | 29.3 units on a scale STANDARD_DEVIATION 0.58 | 26.7 units on a scale STANDARD_DEVIATION 3.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 6 Participants | 3 Participants | 27 Participants |
| Region of Enrollment United States | 20 Participants | 6 Participants | 3 Participants | 29 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 14 Participants | 2 Participants | 3 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 1 / 6 | 0 / 3 |
| other Total, other adverse events | 2 / 20 | 1 / 6 | 0 / 3 |
| serious Total, serious adverse events | 0 / 20 | 0 / 6 | 0 / 3 |
Outcome results
Primary
Flortaucipir Imaging in PSP, CBD and Healthy Volunteers
A PSP/CBD (PSP = progressive supranuclear palsy; CBD = corticobasal degeneration) targeted composite Standardized Uptake Value ratio (SUVr) was calculated as the voxel-weighted average from the regional SUVr values of the left, right, and total globus pallidus and the dentate nuclei of the cerebellum for both the baseline and 9 month PET scans. Additionally, a global cortical Alzheimer's Disease (AD)-targeted cortical SUVr was calculated. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline and 9 month scans
Population: Healthy volunteers did not receive 9 month follow-up scans. 9 month data presented only for those subjects who completed both a baseline and 9 month scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical Baseline | 0.99 standardized uptake value ratio (SUVr) | Standard Deviation 0.03 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus Baseline | 1.62 standardized uptake value ratio (SUVr) | Standard Deviation 0.15 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus Baseline | 1.60 standardized uptake value ratio (SUVr) | Standard Deviation 0.15 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate 9 months | 1.17 standardized uptake value ratio (SUVr) | Standard Deviation 0.11 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus 9 Months | 1.58 standardized uptake value ratio (SUVr) | Standard Deviation 0.13 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate Baseline | 1.17 standardized uptake value ratio (SUVr) | Standard Deviation 0.12 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary 9 Months | 1.37 standardized uptake value ratio (SUVr) | Standard Deviation 0.09 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate Baseline | 1.16 standardized uptake value ratio (SUVr) | Standard Deviation 0.1 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical 9 Months | 0.99 standardized uptake value ratio (SUVr) | Standard Deviation 0.03 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary Baseline | 1.38 standardized uptake value ratio (SUVr) | Standard Deviation 0.1 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus 9 Months | 1.62 standardized uptake value ratio (SUVr) | Standard Deviation 0.15 |
| PSP Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate 9 months | 1.13 standardized uptake value ratio (SUVr) | Standard Deviation 0.11 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate 9 months | 1.11 standardized uptake value ratio (SUVr) | Standard Deviation 0.05 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate Baseline | 1.12 standardized uptake value ratio (SUVr) | Standard Deviation 0.04 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate Baseline | 1.09 standardized uptake value ratio (SUVr) | Standard Deviation 0.04 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate 9 months | 1.08 standardized uptake value ratio (SUVr) | Standard Deviation 0.05 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus Baseline | 1.40 standardized uptake value ratio (SUVr) | Standard Deviation 0.2 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus 9 Months | 1.47 standardized uptake value ratio (SUVr) | Standard Deviation 0.19 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus Baseline | 1.56 standardized uptake value ratio (SUVr) | Standard Deviation 0.32 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus 9 Months | 1.62 standardized uptake value ratio (SUVr) | Standard Deviation 0.4 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary Baseline | 1.29 standardized uptake value ratio (SUVr) | Standard Deviation 0.11 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary 9 Months | 1.32 standardized uptake value ratio (SUVr) | Standard Deviation 0.13 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical Baseline | 0.99 standardized uptake value ratio (SUVr) | Standard Deviation 0.06 |
| CBD Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical 9 Months | 1.00 standardized uptake value ratio (SUVr) | Standard Deviation 0.05 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus Baseline | 1.30 standardized uptake value ratio (SUVr) | Standard Deviation 0.07 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical Baseline | 1.02 standardized uptake value ratio (SUVr) | Standard Deviation 0.02 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate Baseline | 1.08 standardized uptake value ratio (SUVr) | Standard Deviation 0.07 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary Baseline | 1.17 standardized uptake value ratio (SUVr) | Standard Deviation 0.03 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate Baseline | 1.03 standardized uptake value ratio (SUVr) | Standard Deviation 0.12 |
| Healthy Volunteers | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus Baseline | 1.29 standardized uptake value ratio (SUVr) | Standard Deviation 0.06 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate 9 months | 1.12 standardized uptake value ratio (SUVr) | Standard Deviation 0.1 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary Baseline | 1.34 standardized uptake value ratio (SUVr) | Standard Deviation 0.12 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate 9 months | 1.15 standardized uptake value ratio (SUVr) | Standard Deviation 0.1 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical 9 Months | 0.99 standardized uptake value ratio (SUVr) | Standard Deviation 0.04 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Global PSP/CBD Summary 9 Months | 1.36 standardized uptake value ratio (SUVr) | Standard Deviation 0.1 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus Baseline | 1.53 standardized uptake value ratio (SUVr) | Standard Deviation 0.19 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus Baseline | 1.58 standardized uptake value ratio (SUVr) | Standard Deviation 0.21 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Dentate Baseline | 1.14 standardized uptake value ratio (SUVr) | Standard Deviation 0.09 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Dentate Baseline | 1.15 standardized uptake value ratio (SUVr) | Standard Deviation 0.12 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Left Globus Pallidus 9 Months | 1.62 standardized uptake value ratio (SUVr) | Standard Deviation 0.21 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | Right Globus Pallidus 9 Months | 1.55 standardized uptake value ratio (SUVr) | Standard Deviation 0.15 |
| All Subjects | Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | AD Cortical Baseline | 0.99 standardized uptake value ratio (SUVr) | Standard Deviation 0.04 |