To 1) clinically validate the novel PET-tracer [18F]AV1451 for tau pathology as a diagnostic and prognostic marker in tauopathies, 2) to examine the (change in) (regional) binding of [18F]AV1451 across tauopathies, and the relationships between (…
ID
Source
Brief title
Condition
- Encephalopathies
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(Change in) the amount and distribution of specific [18F]AV1451 binding in DLB
and AD
Secondary outcome
- Neuropsychological performance (over time);
- DLB specific questionnaires
- Gray matter volumes on MRI (over time);
- CSF protein levels (over time);
- Amyloid-beta PET tracer binding (when available).
- FDG tracer binding
- EEG measurements
Background summary
The most common cause of dementia, Alzheimer*s disease, is pathologically
characterized by aggregated amyloid-beta and hyperphosphorylated tau proteins.
Several other neurodegenerative diseases that can underlie dementia also
present with tau pathology such as Dementia with lewy bodies.
The success of amyloid PET-tracers such as Pittsburgh compound B,
[18F]Florbetapir, [18F]Flutemetamol and [18F]Florbetaben, prompted the search
for a tau-specific PET-tracer and has led to the recent introduction of the tau
tracer [18F]AV1451. The possibility to visualize and quantify tau pathology in
vivo has the potential to greatly facilitate research on tau pathology inducing
AD dementia and other non-AD dementias. For example, assessment of regional
uptake patterns of tau, which are distinct across tauopathies, may improve
diagnostic accuracy and may help to identify tauopathies in an early stage.
Second, in contrast to Amyloid-beta, the spread of tau-pathology has been shown
to be tightly correlated with neurodegeneration and cognitive deterioration,
indicating that (longitudinal) [18F]AV1451 binding may help to provide insight
into staging of tau pathology and serve as a prognostic marker for disease
progression. Finally, PET-imaging with [18F]AV1451 would contribute to the
development of new tau-targeted treatments by providing a means to identify
applicable patients for clinical trials, and by offering an in-vivo surrogate
marker of tau pathology.
Study objective
To 1) clinically validate the novel PET-tracer [18F]AV1451 for tau pathology as
a diagnostic and prognostic marker in tauopathies, 2) to examine the (change
in) (regional) binding of [18F]AV1451 across tauopathies, and the relationships
between (change in) tracer binding, neurodegeneration and symptoms, and 3) to
explore the predictive value of [18F]AV1451 binding for change over time in
neuropsychological performance.
Study design
The present study is a longitudinal, observational study. The diagnostic
intervention is a PET scan using [18F]AV1451 for in vivo visualisation and
quantification of tau pathology in the human brain. This project builds on a
tracer kinetic model previously developed in another project and aims to
implement [18F]AV1451 in a clinical setting.
Eligible participants will be recruited from the VUmc, Erasmus MC and the UMCU.
For the VUmc, participants will be recruited from the Amsterdam dementia
cohort, consisting of patients of the Alzheimer center of the VU medical
center. These patients have all been screened according to the VUmc
standardized dementia screening protocol including physical examination,
medical history, neuropsychological testing, MRI and laboratory measurements.
In addition, lumbar puncture is performed to obtain measurements of
Amyloid-beta, and tau in CSF for all patients, unless contraindicated. For the
Erasmus medical center, patients recruitment will rely on the study titled
*Early brain changes in frontotemporal dementia* (also known as the FTD-risC
study; protocol number: MEC-2009-409). For the University medical center
Utrecht, patients are primarily recruited from the study titled *Biomarkers in
body fluids of patients with neurodegenerative disorders* (also known as the
Parelsnoer study; protocol number 09-211).
After signing informed consent and screening procedures (physical examination
and if necessary MRI brain), paticipants will be invited to undergo a dynamic
[18F]AV1451 PET scan on a clinical PET-CT scanner and for DLB patients a static
[18F]-FDGPET scan at the VU Medical Center on a PET-CT scanner.
All paticipants will receive annual clinical follow-up that includes
neuropsychological examination according to the same standardized protocols as
performed at baseline examination.
MCI/AD subjects will, >2 years after baseline [18F]AV1451, be asked to undergo
a second [18F]AV1451 PET scan. Additionally, they will be invited to undergo a
lumbar puncture at follow up.
Intervention
Name of compound : 18F-AV-1451(also known as [F-18]T807) Dose: 240 MBq (6.5mCi)
Route of Administration: lntravenous (IV) bolus
Study burden and risks
Risks associated with participation in this study are related to 1) radiation
exposure; 2) idiosyncratic reaction to the tracer ;
3) placement of the arterial and intra-venous catheter; 4) discomfort during
PET scanning; 5) chance findings, and 6) small chance of headache after lumbar
puncture.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria: , - At least 35 years of age
- Subjects must, in the opinion of the principal investigator/attending
neurologist, be able to tolerate the [18F]AV1451 PET scan procedures and be
competent to make a well informed decision to participate in this study..,
Additional inclusion criteria per diagnostic group:, For probable AD dementia
patients;
- A diagnosis of probable AD with at least intermediate likelihood according to
recently proposed NIA-AA criteria27. This will be determined using PET and/or
CSF evidence of A* deposition., For *MCI due to AD* patients;
- Patients must meet clinical criteria for MCI25, and;
- present with positive A* biomarkers on PET and/or CSF., For DLB patients;
- At least 50 years of age
- Patients must be included in the DEvELOP (protocol number 15/548)
- Subjects must, in the opinion of the principal investigator/attending
neurologist, be able to tolerate the [18F] FDG PET scan procedures, For
controls;
- No objective evidence of cognitive impairment as assessed by a
multidisciplinary specialist team;
- normal MRI;
Exclusion criteria
No MRI available or possible
Abnormalities on MRI which may interfere with PET image assessment:
Is or may become pregnant in the first 24h after the PET scan
Relevant history of drug allergy or hypersensitivity
Has ever recieved a tau and/or amyloid-beta targetting agent
Has been injected with a previously administered radiopharmaceutical within 6
terminal half-lives OR the total yearly radiation exposure exceeds 10 mSv;
Has a history of moderate or severe traumatic brain injury (TBI).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-005604-29-NL |
| CCMO | NL55206.029.15 |