This protocol is a follow-up of a previously submitted protocol (Evaluation of [18F]AV-1451 kinetic modelling in patients with Alzheimer*s Disease and healthy controls, protocol nr. 2014.519), in which the optimal (simplified) kinetic model for [18F…
ID
Source
Brief title
Condition
- Encephalopathies
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome is the test-retest variability of the previously defined
simplified tracer kinetic model to quantify specific binding of [18F]AV-1451.
Secondary outcome
not applicable
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, A* 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 A* * 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.
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.
As such, [18F]AV-1451 has great potential as a prognostic marker in preclinical
and clinical stages of AD. The overall aim of this proposal is to fully develop
[18F]AV-1451 as a tau marker that can be used for accurate and early diagnosis
of AD, for prognostic purposes. This requires validation of previously defined
(simplified) kinetic models for [18F]AV-1451 and assessing test-retest
variability of these measures.
Study objective
This protocol is a follow-up of a previously submitted protocol (Evaluation of
[18F]AV-1451 kinetic modelling in patients with Alzheimer*s Disease and healthy
controls, protocol nr. 2014.519), in which the optimal (simplified) kinetic
model for [18F]AV-1451 will be developed. We aim to validate this model, by
assessing test-retest variability. The objectives of this project are:
1) To assess test-retest variability of the previously defined tracer kinetic
model to quantify specific binding of [18F]AV-1451
Study design
This study includes 7 healthy elderly controls and 8 patients with AD or MCI
due to AD. [18F]AV-1451 is injected intravenously and immediately following
injection, a dynamic 60 minute PET scan will be performed. An additional
dynamic 50 minute PET scan will occur approximately 80 minutes following
injection. Procedures are repeated after 1 week.
Study burden and risks
1. Radiation exposure
Subjects receive 2 PET-scans with [18F]AV-1451. Before every scan, a low dose
CT scan is made. The radiation exposure is 12,4 mSv each year. The total amount
of radiation for this study is 12,4 mSv.
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 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
Healthy volunteers:
1. At least 50 years of age;
2. Have no evidence of cognitive impairment as indicated by a cognitive neurologist;
3. Subjects, who in the opinion of the principal investigator, can tolerate the [18F]AV1451 PET scan procedures.;MCI due to AD subjects:
1. At least 50 years of age;
2. Have a clinical diagnosis of MCI (Albert, 2011)
3. Have positive A* biomarkers on PET and/or CSF
4. Have a Mini Mental State Examination (MSSE) of 18 or higher;
5. Subjects, who in the opinion of the principal investigator, can tolerate the [18F]AV1451 PET scan procedures.;AD patients:
1. At least 50 years of age;
2. Have a clinical diagnosis of probable AD (McKhann, 2011)
3. Have a Mini Mental State Examination (MMSE) of 18 or higher;
4. Subjects, who in the opinion of the principal investigator, can tolerate the [18F]AV-1451 PET scan procedures.
Exclusion criteria
1. Has contra indications for MRI scanning and therefore can not receive brain MRI
2. Has evidence of structural abnormalities such as major stroke or mass on MRI that is likely to interfere with interpretation of a PET scan;
3. Has a history of severe traumatic brain injury (TBI);
4. Is a female of childbearing potential who is not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception for up to 24 hours after scanning procedures. Females of childbearing potential must not be pregnant or breastfeeding at screening.
5. Has a relevant history of severe drug allergy or hypersensitivity (relevant severe drug allergies should be determined by the Principal Investigator or Co-Principal Investigator, and any questions about a subject*s eligibility can be directed to Avid Radiopharmaceuticals Inc.);
6. 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.
7. Has been injected with a previously administered radiopharmaceutical within 6 terminal half-lives OR when total yearly radiation exposure exceeds 10 mSv.
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 | EUCTR2015-004230-10-NL |
| CCMO | NL54572.029.15 |