Frontotemporal Dementia (FTD), Frontotemporal Lobar Degeneration (FTLD), Tauopathies
Conditions
Keywords
FTLD, FTD
Brief summary
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
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).
Interventions
DRUG18F-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.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SUVR of 18F-AV-1451 | Baseline, 12-month follow up | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 18F-AV-1451 Subjects 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.
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. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | 18F-AV-1451 |
|---|---|
| Age, Customized 18-21 years | 0 Participants |
| Age, Customized 22-29 years | 1 Participants |
| Age, Customized 30-39 years | 1 Participants |
| Age, Customized 40-49 years | 0 Participants |
| Age, Customized 50-59 years | 4 Participants |
| Age, Customized 60-69 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 4 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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.
Time frame: Baseline, 12-month follow up
Population: 5 out of 7 subjects had data collected and analyzed (evaluable repeat imaging after 12 months).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 18F-AV-1451 - Non-carriers | SUVR of 18F-AV-1451 | Inferior temporal cortex (Cerebellar crus) | 1.07 standardized uptake value ratio (SUVR) |
| 18F-AV-1451 - Non-carriers | SUVR of 18F-AV-1451 | Inferior temporal cortex (PERSI) | 1.03 standardized uptake value ratio (SUVR) |
| 18F-AV-1451 - Carriers | SUVR of 18F-AV-1451 | Inferior temporal cortex (Cerebellar crus) | 1.26 standardized uptake value ratio (SUVR) |
| 18F-AV-1451 - Carriers | SUVR of 18F-AV-1451 | Inferior temporal cortex (PERSI) | 1.34 standardized uptake value ratio (SUVR) |