The main objective is to quantify neuroinflammation using [11C]SMW139 PET-scans in subjects along the AD continuum and age/sex-matched cognitively unimpaired subjects.
ID
Source
Brief title
Condition
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the spatial distribution of specific [11C]SMW139
binding in patients with AD compared to age-matched cognitively unimpaired
subjects.
Secondary outcome
Secondary endpoints include the association of (spatial) [11C]SMW139 specific
binding to neuropsychological performance and neurodegeneration.
Background summary
Although amyloid plaques and neurofibrillary tangles (tau) are still considered
the defining features of Alzheimer*s Disease (AD), microglia-mediated
inflammation, known for decades to be present in AD, has finally taken
centre-stage in research on its pathogenesis. Indeed, APOE and TREM2, two major
AD risk genes, are important parts in the microglial response. The fact that
many AD risk genes converge on microglial response pathways indicates their
central role in the disease pathogenesis. With [11C]SMW139 positron emission
tomography (PET) we can identify if activated microglia in AD are indeed
pro-inflammatory, e.g. neurotoxic and as such a potential treatment target.
Study objective
The main objective is to quantify neuroinflammation using [11C]SMW139
PET-scans in subjects along the AD continuum and age/sex-matched cognitively
unimpaired subjects.
Study design
Observational case-control study with longitudinal follow-up
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 intra-venous
and intra-arterial catheters, 4) discomfort during scanning, 5) blood sampling;
6) incidental findings. There is no direct individual benefit to be gained from
participating in the current study. However, an indirect effect in the future
is plausible for participants with AD, since more knowledge about the
involvement of pro-inflammatory microglia in AD may lead to novel therapeutic
discoveries.
De Boelelaan 1118
Amsterdam 1081HV
NL
De Boelelaan 1118
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Group 1: subjects along the AD continuum
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1. Be along the AD continuum, defined as having positive biomarker evidence
(CSF or PET) for the presence of Aβ pathology.
2. At least 50 years of age;
3. Subjects must, in the opinion of the principal investigator/attending
neurologist, be able to tolerate study procedures and be competent to make a
well-informed decision to participate in this study;
4. Signed informed consent for Amsterdam Dementia Cohort (2016.061);
Group 2: cognitively unimpaired subjects
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1. Have biomarker evidence (CSF or PET) for the absence of Aβ pathology;
2. Have no objective cognitive impairment as determined by a neuropsychologist
or neuropsychological testing;
3. At least 50 years of age;
4. Subjects must, in the opinion of the principal investigator/attending
neurologist, be able to tolerate study procedures and be competent to make a
well-informed decision to participate in this study.
5. Signed informed consent for Amsterdam Dementia Cohort (2016.061);
Exclusion criteria
1. Has contra indications for MRI scanning and therefore cannot receive a brain
MRI;
2. Has evidence of (gross) structural abnormalities such as major stroke or
mass on MRI that is likely to interfere with interpretation of PET scan;
3. Inability to undergo PET-CT with administration of radioligand [11C]SMW139;
4. 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 and at imaging;
5. Has a relevant history of severe drug allergy or hypersensitivity. This
includes (but is not limited to) hay fever, allergies to cats and dogs, and
dust mite allergy. Other relevant severe drug allergies or hypersensitivities
should be evaluated by the Principal Investigator;
6. Has ever participated in an experimental study with a tau, amyloid or
neuroinflammation targeting agent, unless it can be documented that the subject
received only placebo during the course of the trial;
7. History of any clinically significant cardiovascular, endocrinology,
hematologic, hepatobiliary, immunologic, inflammatory, metabolic, urologic,
pulmonary (including asthma), neurologic (with the exception of AD),
psychiatric, renal or other major disease, as determined by the principal
investigator;
8. In male subjects Hb < 8.0 g/dL, in female subjects Hb < 7.0 g/dL;
9. Has been injected with a previously administered radiopharmaceutical within
6 terminal half-lives OR when total yearly radiation exposure exceeds 10 mSv;
10. Has a history of severe traumatic brain injury (TBI);
11. The following medications during the study and 4 weeks prior to [11C]SMW139
PET:
a. Use of anticonvulsant medications;
b. Anti-inflammatory medications (e.g. chronic NSAID use);
c. Other medications that, in the opinion of the investigator, may interfere
with the study.
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 | EUCTR2022-002481-32-NL |
| CCMO | NL81807.029.22 |