Determination of possible Alzheimer pathology in the brain and to follow-up participants over time (by means of another research protocol). In addition, its [18F]-label with a half-life of 110 minutes will enable use in hospitals without an on-site…
ID
Source
Brief title
Condition
- Neurological disorders NEC
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The outcome measure, amyloid deposition (both visual and quantitative ),
acquired with [18F]AV-45 PET scans in a memory clinic patient cohort.
Quantification is performed with optimized kinetic models acquired in another
research Florbetapir protocol (kinetic modelling of 18 F labeled amyloid
tracers).
Secondary outcome
Secondary study parameters are the concordance of [18F]AV-45 PET with MRI
markers (MTA) and with CSF markers (A* 1-42, total tau and p-tau 181) will be
assessed by binary rating (e.g. *normal* or *abnormal*) and amyloid tracer
quantification for each of these measures. Furthermore, at baseline dementia
severity and neuropsychological measures will be obtained to allow analysis of
associations with continuous measures of cognitive impairment to determine the
prognostic value of [18F]AV-45 PET.
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. Despite
encouraging results, the short half-life (20 minutes) of the 11C isotope limits
the utility of 11C-PIB as a tool for community based diagnostic screening and
therapeutic evaluation.
In contrast, [18F]AV-45 is a novel amyloid binding agent (Zhang et al. 2005;
Zhang et al. 2006) labelled with 18F. Since 18F has a radioactive half-life of
110 minutes, regional preparation and shipping of doses is possible, thereby
reducing the cost and increasing the number of potential imaging centers. In
addition, [18F]AV-45 is one of the first tracers fulfilling FDA requirements of
postmortem verification and correlation of the specific binding and as such
will probably be the first tracer to be used in drug development programs.
Study objective
Determination of possible Alzheimer pathology in the brain and to follow-up
participants over time (by means of another research protocol). In addition,
its [18F]-label with a half-life of 110 minutes will enable use in hospitals
without an on-site cyclotron, greatly enhancing its clinical applicability. The
present study is designed to evaluate tracer kinetics of [18F]AV-45 and to
investigate its clinical diagnostic and prognostic value in early cognitive and
memory complaints.
Study design
The clinical prognostic study exists of one PET scan. This study includes 250
cognitively normal subjects. Subjects will undergo a PET-scan after intravenous
administration of the [18F]AV-45 tracer twice, over the course of 2 years.
Analysis will be perfomed to investigate whether there is significant amyloid
deposition in the brain.
Intervention
Intervention with a diagnostic medicine.
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 and intra-arterial (only in kinetische modeling study including
15 AD patients and 15 controls) catheter; 4) discomfort during scanning, and 5)
blood sampling.
1) Administration of 185 MBq [18F]Florbetapir will result in a whole body
effective dose of 3.5 mSv according to the GE-067study (see IB Edition 6/ March
2012). 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
cameras (both PET and MRI) 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.
De Boelelaan 1118
Amsterdam 1081 HZ
NL
De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
- age >45
- Written informed consent
- Weight >50 kg , - Able to tolerate 70-minute scanning
- No objective cognitive impairment (i.e. no diagnosis of dementia, mild cognitive impairment, psychiatric or neurological disorder explaining cognitive complaints).
- MMSE ><= 18
Exclusion criteria
Patients who
1. Have a current a major psychiatric disorder, such as psychosis, schizophrenia, severe personality disorder or depression with vital signs, abuse of alcohol or other substances. Or patients who have a neurological disorder, such as Parkinson's disease, symptomatic stroke, mental retardation.
2. Are women of childbearing potential who are not surgically sterile, not refraining
from sexual activity or not using reliable methods of contraception. Women of
childbearing potential must not be pregnant (negative urine *-hCG at the time of
screening and negative urine *-hCG on the day of imaging) or breast feeding at
screening. Women 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 florbetapir (18F);
3. Have 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. If a subject has a history of severe drug allergies, it may be
dangerous for them to participate in a study with a novel compound);
4. 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 the subject received no investigational medication (yet) or only placebo during the course of the trial;
5. Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior
to the study imaging session.
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 | EUCTR2012-001599-12-NL |
| CCMO | NL39189.029.13 |