Tau Imaging in Subjects With Progressive Supranuclear Palsy, Corticobasal Degeneration and Healthy Volunteers

Phase 1

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

Cognitively Healthy Volunteers

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

Arm && Interventions

Group	Intervention	Description
PSP Subjects	Brain PET scan	Amyloid negative subjects with PSP receiving a flortaucipir PET scan at baseline and at 9 months.
CBD subjects	Brain PET scan	Amyloid negative subjects with CBD receiving a flortaucipir PET scan at baseline and at 9 months.
Healthy volunteers	Brain PET scan	Healthy volunteers receiving a flortaucipir PET scan at baseline.
PSP Subjects	Flortaucipir F18	Amyloid negative subjects with PSP receiving a flortaucipir PET scan at baseline and at 9 months.
CBD subjects	Flortaucipir F18	Amyloid negative subjects with CBD receiving a flortaucipir PET scan at baseline and at 9 months.
Healthy volunteers	Flortaucipir F18	Healthy volunteers receiving a flortaucipir PET scan at baseline.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method

Locations (5): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
UCSD Movement Disorder Clinic
🇺🇸
La Jolla, California, United States
Molecular Neuroimaging
🇺🇸
New Haven, Connecticut, United States
UCSF Neurosciences Clinical Research Unit
🇺🇸
San Francisco, California, United States
Perelman School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States