Tau PET Imaging With 18F-AV-1451 in Subjects With MAPT Mutations

Study Overview
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Brief Summary
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The study will investigate the ability of a new PET tracer, 18F-AV-1451, to detect depositions of a protein, called tau, in the brains of people with a mutation in the tau gene that causes deposition of the protein, and in people without the mutation. Up to three 18F-AV-1451 scans will be performed (one per year) on control subjects without MAPT mutations, presymptomatic mutation carriers, and symptomatic mutation carriers.

Detailed Description
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Approximately 40% of cases of Frontotemporal lobar Degeneration (FTLD) are also associated with abnormal deposition of tau protein. The purpose of this study is to image MAPT mutation carriers and their non-carrier relatives in order to study the use of this tracer as a biomarker in Frontotemporal Lobar Degeneration with tau deposition (FTLD-tau).

Official Title
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Tau PET Imaging With 18F-AV-1451 in Subjects With MAPT Mutations

Conditions
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Frontotemporal Lobar Degeneration (FTLD), Frontotemporal Dementia (FTD), Tauopathies

Intervention / Treatment
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* Drug: 18F-AV-1451


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Members of families with established MAPT mutations, who either have the capacity to consent to participate in the protocol, or else have designated a surrogate/proxy to consent to participate in this study Exclusion Criteria: Unwillingness to participate Usage of medication which significantly prolongs QT interval Pregnancy or plans for pregnancy within 90 days after participating in study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-AV-1451<br>Subjects who are microtubule associated protein tau (MAPT) family carriers and non-carriers will receive 18F-AV-1451 by injection, and undergo a Positron Emission Tomography (PET) scan, which will then be qualitatively analyzed to examine tau deposition in the brain. | Drug: 18F-AV-1451<br>* A single injection of up to 10 millicuries of 18F-AV-1451 will be administered to subjects, followed by a 20-minute PET scan.<br>* Other names: [18F]AV-1451;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SUVR of 18F-AV-1451 | Regional tau deposition will be measured as standardized uptake value ratio (SUVR) of 18F-AV-1451. SUVR (80-100 min post-injection) for 18F-AV-1451 will be calculated two ways: 1) using cerebellar crus as a reference region, and 2) using the Parametric Estimation of Reference Signal Intensity (PERSI) method to create individual white matter reference regions. Binding in the inferior temporal lobe/cortex was used as the primary outcome. | Baseline, 12-month follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FTD, FTLD