Multicenter Study of Tau Imaging With the Use of [18F]MK-6240 Tracer in Individuals at Risk for and With Autosomal Dominant Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Study the spatial (both local and distributed) changes of tau deposition (using [18F]MK-6240).
研究概览
简要总结
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •Male or female participants, at least 18 years of age.
- •Cognitively normal, or with mild dementia, as assessed clinically.
- •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).
- •Pre-menopausal women will undergo a urine pregnancy test within 24 hours of drug administration. -
排除标准
- •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).
- •Is deemed likely unable to perform the imaging procedures for any reason.
- •Has hypersensitivity to [18F]MK-6240or any of its excipients.
- •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.
- •Severe claustrophobia.
- •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.
- •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.
- •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.
- •http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.
- •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. -
研究组 & 干预措施
MK 6240
干预措施: MK 6240 (Drug)
结局指标
主要结局
Study the spatial (both local and distributed) changes of tau deposition (using [18F]MK-6240).
时间窗: 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 temporal dynamics of tau deposition (using [18F]MK-6240).
时间窗: 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 relationship between in vivo tau deposition and neuropathology.
时间窗: 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.
次要结局
未报告次要终点
研究者
Tammie L. S. Benzinger, MD, PhD
Professor of Radiology and Neurological Surgery
Washington University School of Medicine