In the present study, we aim to estimate concordance between two biomarkers developed to interrogate the presence of brain amyloid deposition. This includes a new amyloid PET-tracer, [18F]Flutemetamol, and a CSF biomarker The objective of the…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome measures are the concordance (diagnostic agreement of reported
brain amyloid status) between [18F]Flutemetamol PET and a range of CSF
tau:abeta1-42 ratio values that meet independently-defined minimum criteria for
a binary classifier of AD (sensitivity * 0.8, specificity >0.6). This range of
CSF threshold values will be determined in a separate study currently underway,
using additional independently collected CSF samples. Secondary outcome is the
concordance between PET amyloid status and routine CSF abeta 1-42, total tau
and p-tau 181 values.
Secondary outcome
Secondary outcome is the concordance between PET amyloid status and routine CSF
abeta 1-42, total tau and p-tau 181 values.
Background summary
Neuropathologically, Alzheimer*s Disease (AD) is characterized by amyloid
plaques and neurofibrillary tangles. Development of the positron emission
tomography (PET) tracer [11C]Pittsburgh compound-B ([11C]PIB) has for the first
time enabled the visualization of amyloid-beta (A*) in vivo, and evidence shows
high sensitivity and specificity in separating AD from controls.
However, [11C]PIB-PET can only be used where an on-site cyclotron is available
for production, hampering its widespread implementation. [18F]-tracers, which
do not require on-site production are therefore more suitable to be used by
many more centers and enable studying the discriminatory value in the clinical
setting.
In parallel to amyloid PET tracers, CSF-based biomarkers reflecting
abnormalities of amyloid processing in AD brain have been developed and refined
for clinical use. Both CSF and PET-based biomarkers are expected to prove
useful in defining patient populations appropriate for treatment with
amyloid-targeting disease modifying therapy. However, the degree of concordance
between specific PET- and CSF-based amyloid diagnostic measurements as proxy
for AD pathology is not well established.
Study objective
In the present study, we aim to estimate concordance between two biomarkers
developed to interrogate the presence of brain amyloid deposition. This
includes a new amyloid PET-tracer, [18F]Flutemetamol, and a CSF biomarker
The objective of the current study will be to compare [18F]Flutemetamol PET
imaging measures of brain amyloid to protein measurements in CSF.
Study design
Prospective, observational study
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 an
intra-venous catheter; 4) discomfort during scanning; 5) lumbar puncture
procedure risk.
1) Administration of 185 MBq [18F]Flutemetamol will result in a whole body
effective dose of 4.1 mSv. For comparison, the natural background radiation
dose in the Netherlands gives an annual dose of 2 - 2.5 mSv. Thus, the total
radiation exposure of the total PET procedure is within an acceptable range of
a yearly (unnatural) radiation exposure with a maximum of 10 mSv. In case of
previous exposure to radioactivity, subjects will be eligible if the yearly
cumulative dose due to exposure to radiation remains below 10 mSv.
2) Idiosyncratic reaction to the tracer
The injected mass of [18F]Flutemetamol PET used in this study is negligible.
[18F]Flutemetamol PET is a radiotracer that have been used in humans. Side
effects have never been reported at the tracer doses used in PET studies. A
physician will be available during each injection of the radiotracer.
3) Intravenous cannulation
There is a very small risk of infection and bleeding associated with
intravenous catheters, which are prevented by proper techniques.
4) Discomfort during scanning
It may be uncomfortable to lie motionless in the PET camera and it may cause
some subjects to feel anxious. Subjects will be made acquainted with the
surroundings beforehand. Our staff will be available to provide support, reduce
anxiety, optimise the comfort of the subject and remove the subject from the
scanner if requested.
5) LP is performed routinely during screening at VUmc Alzheimer Center, unless
patient is not willing to undergo LP or any contra-indications exist. The
withdrawal of an extra 2 ml for this protocol is deemed not to cause extra
discomfort
De Boelelaan 1118
Amsterdam 1007 MB
NL
De Boelelaan 1118
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
Each subject :
- must be * 50 to * 85 years of age;
- is seen at the memory clinic of the VUmc Alzheimer Center upon referral of another clinician and follows the routine screening procedure;
- must have results of routine clinical laboratory tests including a complete blood count (CBC) a physical examination, vital signs within normal limits or clinically acceptable to the investigator within 60 days prior to enrollment;
- must have signed (the study specific)informed consent form, which covers the scope and nature of this agreement before screening assessments;
- must have given additional cerebrospinal fluid for this study and checked "Yes" to the following questions located on page 2 of the general informed consent form of the Alzheimer Center; 'I give my consent for the storage and use of my coded medical information' and 'I give my consent for the collection, storage and provision of coded samples of my cerebrospinal fluid to the Alzheimer*s Center Biobank and the String of Pearls Initiative Parelsnoer Initiatief for the purposes outlined in the information'.;- The maximum time frame between LP and PET scanning is 6 months
Exclusion criteria
Patients who
- are considered medically unstable;
- require additional laboratory tests or workup between enrolment and completion of the PET scan;
- have a clinically significant infectious disease, including Acquired Immunodeficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection;
- are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days prior to the PET scan;
- have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, *-secretase or *-secretase inhibitor) unless it can be documented that he subject received only placebo during the course of the trial;
- have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the PET scan;
- are females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Females of childbearing potential must not be pregnant (negative serum *-hCG at the time of screening and negative urine *-hCG on the day of imaging) or breast feeding at screening. Females must avoid becoming pregnant, and must agree to refrain from sexual activity or to use reliable contraceptive methods such as prescribed birth control or IUD for 24 hours following administration of [18F]Flutemetamol;
- are claustrophobic;
- have abnormalities on MRI other than white matter changes or an incidental small lacunar lesion which may can affect Flutemetamol PET scan reading.
- have donated blood within 3 months before the scan day;
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 | EUCTR2013-003733-15-NL |
| CCMO | NL46225.029.13 |