Alzheimer Disease, Healthy Volunteers, Progressive Supranuclear Palsy
Conditions
Keywords
HV, AD, PSP
Brief summary
The overall goal of this protocol is to evaluate \[18F\]MNI-958 also known as APN-0000455 or PM-PBB3, a tau targeted radiopharmaceutical.
Detailed description
The overall goal of this protocol is to evaluate \[18F\]MNI-958 also known as APN-0000455 or PM-PBB3, a tau targeted radiopharmaceutical. The specific objectives are: * To measure the dynamic uptake and washout of \[18F\]MNI- 958 in brain using positron emission tomography (PET) in patients with Alzheimer's disease, Progressive Supranuclear Palsy and healthy volunteers. * To measure blood metabolites of \[18F\]MNI-958 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input. * To obtain test/retest reliability of the tracer binding parameters in patients with Alzheimer's disease, Progressive Supranuclear Palsy and healthy volunteers. * To acquire safety data following injection of \[18F\]MNI-958.
Interventions
DRUG[18F]MNI-958
Subjects will undergo PET imaging using \[18F\]MNI-958, a PET radioligand for imaging tau.
Sponsors
Invicro
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
(for all subjects): * Written informed consent must be obtained before any assessment is performed. * Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of childbearing potential, must commit to use a barrier contraception method for the duration of the study. * Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male subjects for the study duration. * Male subjects must not donate sperm for the study duration. * Willing and able to cooperate with study procedures Inclusion criteria for healthy volunteer subjects * Males and females aged ≥50 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the \[18F\]MNI-958 imaging visit. * No cognitive impairment from neuropsychological battery as judged by the investigator * Have screening or prior (in the last 90 days) amyloid PET imaging demonstrating no significant amyloid binding based on qualitative (visual read). * No family history of Alzheimer's disease or neurological disease associated with dementia * Have a CDR global score=0 * Have an MMSE score ≥28 * Willing and able to cooperate with study procedures Inclusion criteria for subjects with a diagnosis of probable Alzheimer's disease (AD): * Males and females aged 50 to 80 years. * Have probable Alzheimer's disease dementia, based on the NINCDS/ADRDA and DSM-IV criteria, with mild severity and amnestic presentation * Have a CDR score ≥ 0.5 at screening * Have a MMSE score between ≤ 28. * Have screening or prior (in the last 12 months) amyloid PET imaging demonstrating amyloid binding based on qualitative analysis (visual read). Amyloid PET imaging results will be shared with participants, and scans may be used by participants for future research use. * A brain MRI that supports a diagnosis of AD, with no evidence of significant neurologic pathology. * Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before screening visit. * The subject has an appropriate caregiver capable of accompanying subject on all visits. * Signed and dated written informed consent obtained from the subject and the subject's legally authorized representative or caregiver (if applicable). Inclusion criteria for subjects with a diagnosis of Progressive Supranuclear Palsy (PSP) * Males and females aged 50 to 90 years. * Has a clinical diagnosis of probable PSP based on the NINDS and Society for PSP (NINDS-PSP) criteria (Litvan, et al 1996). * Have screening or prior DaTscan SPECT imaging demonstrating evidence of dopamine transporter deficit based on visual read. * A brain MRI that supports a diagnosis of PSP, with no other evidence of significant neurologic pathology * Medications taken for symptomatic treatment of PSP must be maintained on a stable dosage regimen for at least 30 days before screening visit. * The subject has an appropriate caregiver capable of accompanying subject, if necessary. * Signed and dated written informed consent obtained from the subject and the subject's legally authorized representative or caregiver (if applicable).
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tracer uptake will be evaluated in regions of interest for analysis of regional [18F]MNI-958 binding/uptake and expressed in SUV by using established methods for normalization for 4 AD, 7 PSP, and 3 HV subjects. | 1 year | Target regions of interest in the standard volume of interest (VOI) template, will be used for tracer uptake quantitation of potentially increased binding to tau pathology will correspond in particular to the cortical regions of the brain. Descriptive statistics will be applied to describe the tau deposition by region as measured by \[18F\]MNI-958. |
Countries
United States
Outcome results
None listed