Alzheimer Disease
Conditions
Keywords
tau, PET, MK 6240, ADAD
Brief summary
The recent development of a PET tracer,\[18F\]MK-6240(an\[18F\]tau imaging agent,CerveauTechnologies)that has high affinity for the human phosphorylated tau deposits in AD brain offers new opportunities to investigate tau pathology. The investigators will evaluate this imaging agent in individuals from families with a known Autosomal Dominant Alzheimer's Disease (ADAD) mutation. This study of tau PET using \[18F\]MK-6240 is performed in conjunction with DIAN and DIAN Extended Registry (DIAN-EXR).
Interventions
DRUGMK 6240
PET tracer, \[18F\]MK-6240 (an\[18F\]tau imaging agent,CerveauTechnologies)that has high affinity for the human phosphorylated tau deposits in AD brain offers new opportunities to investigate tau pathology.(Hostetler, Walji et al. 2016, Lohith, Bennacef et al. 2016, Walji, Hostetler et al. 2016, Lohith, Bennacef et al. 2017, Neelamegam, Yokell et al. 2017).We will evaluate this imaging agent in individuals from families with a known Autosomal Dominant Alzheimer's Disease (ADAD) mutation. The planned dosage for \[18F\]MK-6240 is a single intravenous bolus injection of 185 MBq (5.0 mCi) in a large peripheral vein followed by a 10 mL normal saline (0.9% NaCl) flush.
Sponsors
Tammie L. S. Benzinger, MD, PhD
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Participants have met all eligibility criteria for enrollment into the Dominantly Inherited Alzheimer's Network (DIAN) and DIAN Extended Registry (DIAN EXR) study enrollment criteria. 2. Male or female participants, at least 18 years of age. 3. Cognitively normal, or with mild dementia, as assessed clinically. 4. Participant is able and willing to undergo testing (magnetic resonance imaging (MRI)or computed tomography (CT), PET, radioactive tracer injection; forthose unable to undergo MRI, CT will be used to generate regions-of interest). 5. Pre-menopausal women will undergo a urine pregnancy test within 24 hours of drug administration. -
Exclusion criteria
1. Has any condition that, in the Investigator's opinion, couldincrease risk to the participant, limit the participant's ability to tolerate the experimental procedures, or interfere with the collection/analysis of the data (for example, participants with severechronic back pain might not be able to lie still duringthe scanning procedures). 2. Is deemed likely unable to perform the imaging procedures for any reason. 3. Has hypersensitivity to \[18F\]MK-6240or any of its excipients. 4. Contraindications to PET, PET-CT or MR(e.g. electronic medical devices, inability to lie still for long periods) that make it unsafe for the individual to participate. 5. Severe claustrophobia. 6. Women who are currently pregnant or breast-feeding, and women who do not agree to use reliable contraception, or to refrain from sexual activity for 24 hours following administration of the \[18F\]MK-6240injection will be excluded from the study. 7. Currently participating in any research studyreceiving an active study medication for AD, an investigational drug, device, imaging, or placebo within the past 30 days before screening, and throughout this clinical trial up to 2-weeks past any study-related procedures. 8. Other than the DIAN study, current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the US Code of Federal Regulations (CFR) Title 21 Section 631.1. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1. It is the responsibility of each site to confirm the date of the most recent PET scan and to work within the guidelines of the local Radioactive Drug Research Committee (RDRC) regarding the imaging interval. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study the temporal dynamics of tau deposition (using [18F]MK-6240). | 12 years from enrollment | Aim 3 multivariate linear regression models will be implemented within the general linear mixed model framework and estimated using restricted maximum likelihood estimation. This approach allows for the estimation of the association between \[18F\]MK-6240 and tauopathy measures across all brain regions to be studied in a single model, by considering the dependency in the plaque measures caused by multiple brain regions being nested within a single patient. |
| Study the spatial (both local and distributed) changes of tau deposition (using [18F]MK-6240). | 12 years from enrollment | Using novel mathematical models, we will correlate the topography of tau PET with both cross-sectional and longitudinal spatial patterns seen with other imaging biomarkers (Aβ PET and MRI \[structuraland functional\]). |
| Study the relationship between in vivo tau deposition and neuropathology. | 12 years from enrollment | We will perform quantitative measures of cortical tauopathy NFT, NP, and neuropil thread (NT) burden in twenty-five brain areas using tau-immunostained sections and automated stereological methods. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTammie Benzinger, MD, PhD
Washington University School of Medicine
Outcome results
None listed