Primary objective:To explore the natural time course of specific [18F]AV-1451 binding in patients with subjective cognitive decline after two and four year follow upa. To compare rate of change in [18F]AV-1451 binding according to baseline amyloid…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change of [18F]AV-1451 binding in time
Secondary outcome
1. Amyloid positivity, as measured by [18F]Florbetapir PET scan
2. Cognitive fucntioning in neuropsychological testing
3. Baseline grey matter atrophy on MRI
4. Baseline CSF measures of amyloid-beta 1-42, total tau, phosphorylated tau
Background summary
Alzheimer*s disease (AD) is the most common cause of dementia in the elderly.
Current biomarkers frequently used to probe AD pathology encompass markers of
amyloid pathology. However, the other core pathological component of AD, tau
pathology, is key to take into account when studying AD. First, Aβ plaques are
only moderately correlated with cognition, while the severity of cognitive
impairment is highly associated with the burden of neocortical neurofibrillary
tangles (NFTs) with hyperphosporylated tau. Second, several studies have
suggested that tau - and not Aβ - is the first neuropathological sign of AD.
Finally, approximately a quarter of cognitively normal subjects show abnormal
neurodegenerative markers while amyloid PET and/or CSF are normal. These
subjects progress frequently to MCI of dementia, suggesting a different
underlying pathology, such as tau.
Patients with subjective cognitive decline (SCD) are those who present with
cognitive complaints, but perform normally after thorough investigation.
Longitudinal studies show SCD is a risk factor for future cognitive decline.
This means a cohort of patients with subjective complaints may be enriched for
incipient AD. Therefore, these subjects form an ideal population to study the
incidence and time course of changes in AD hallmark pathologies.
Tau pathology can now be studied in-vivo with the PET tracer [18F]AV-1451.
Binding of this tracer co-localizes with NFTs, but not with amyloid plaques,
and there is increased [18F]AV-1451 uptake in AD patients compared to controls.
Studying tau pathology in a longitudinal fashion offers a new perspective on
its prevalence, distribution and natural time course. This is relevant not only
for a better understanding of AD pathogenesis, but [18F]AV-1451 has also
potential as a surrogate outcome measure in clinical trials tailored to reduce
tau burden.
Study objective
Primary objective:
To explore the natural time course of specific [18F]AV-1451 binding in patients
with subjective cognitive decline after two and four year follow up
a. To compare rate of change in [18F]AV-1451 binding according to baseline
amyloid status
b. To compare rate of change in [18F]AV-1451 binding according to clinical
progression over time
Secondary objectives:
1. To investigate the relationship between tau pathology, as measured with
[18F]AV-1451, and amyloid load, as measured with [18F]Florbetapir
2. To investigate the correlation between [18F]AV-1451 binding and
neuropsychological performance
3. To investigate the correlation between [18F]AV-1451 binding and grey matter
volume on MRI
4. To investigate the correlation between [18F]AV-1451 binding and CSF measures
of amyloid-beta 1-42, total tau and phosphorylated tau
Study design
This is a prospective, longitudinal observational study
Study burden and risks
1. Radiation exposure
Subjects receive 5 PET-scans: on baseline 1 [18F]AV-1451 scan, after 2 and 4
year follow up [18F]AV-1451 and [18F]Florbetapir scan. Before every scan, a low
dose CT scan is made. The radiation exposure is 13.6 mSv each year.
2. Idiosyncratic reaction to the tracer
The following adverse effects have been reported: headache, diarrhea, dysguesia
3. Placement of the intra-venous catheter
There is a very small risk of infection and bleeding associated with
intravenous catheters
4. Discomfort during scanning
It may be uncomfortable to lie motionless in the PET scanner. Subjects may
expierence myalgia.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Clinically diagnosed with 'subjective cognitive decline' after the
standardized dementia screening performed at the VUmc Alzheimer Center
- At least 50 years of age
- Enrollment in the FIAD cohort (protocol nr 13-256)
- Have received or will receive a [18F]Florbetapir PET scan 90 days before or
after the [18F]AV-1451 PET scan
Exclusion criteria
- Has contraindications for MRI scanning and therefore has not received brain
MRI
- Has evidence for structural abnormalities such as major stroke or mass on MRI
that is likely to interfere with interpretation of PET scan
- Is a woman of childbearing potential who is not surgically sterile, not
refraining from sexual activity or not using reliable methods for
contraception. Women of childbearing potential must not be pregnant or breast
feeding at screening.
- Has a relevant history of severe drug allergy or hypersensitivity. Relevant
severe drug allergies should be determined by the Principal Investigator or
Co-Prinicipal Investigator, and any questions about a subject's eligibility can
be directed to Avid Radiopharmaceuticals Inc.;
- Has ever participated in an experimental study with a tau or amyloid
targeting agent, unless it can be documented that the subject received only
placebo during the course of the trial;
- Has been injected with a previously administered radiopharmaceutical within 6
terminal half-lives OR when total yearly radiation exposure exceeds 10 mSv
- Has a history of 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 | EUCTR2015-003705-42-NL |
| CCMO | NL54520.029.15 |