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

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.

Study Overview

• Status: Completed
• Conditions: Tauopathies; Frontotemporal Dementia (FTD); Frontotemporal Lobar Degeneration (FTLD)
• Intervention / Treatment: Drug: 18F-AV-1451

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Morton A. Kreitchman PET Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 18F-AV-1451; 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; A single injection of up to 10 millicuries of 18F-AV-1451 will be administered to subjects, followed by a 20-minute PET scan.; Other Names: [18F]AV-1451

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Edward Huey, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): November 25, 2018
• Study Completion (Actual): November 25, 2018

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: February 4, 2016
• First Posted (Estimate): February 8, 2016

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: FTD; FTLD
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Language Disorders; Communication Disorders; Speech Disorders; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Tauopathies; Frontotemporal Lobar Degeneration
• Other Study ID Numbers: AAAP4551; R01NS076837 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified clinical characteristics subjects such as age, mutation and rating scale/score of mental state in the manuscript.
• IPD Sharing Time Frame: Availability of the manuscript through journal editors
• IPD Sharing Access Criteria: Availability of the manuscript through journal editors

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No