The aim of this study is to determine NET availability in patients with neurodegenerative diseases to characterize NA system degeneration in people with Alzheimer's disease, Parkinson's disease (with and without dementia) and with…
ID
Source
Brief title
Condition
- Other condition
- Chromosomal abnormalities, gene alterations and gene variants
- Movement disorders (incl parkinsonism)
Synonym
Health condition
neurodegeneratieve aandoeningen (ziekte van Alzheimer)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Several values will be computed from the PET data and between group results are
statistically compared: NET binding potentials (BP) will be computed for each
region of interest (LC and projection areas), .and between-group differences
will be investigated.
Secondary outcome
Correlations between results on the MMSE, NPI, PSQI, ADL en iADL scales and the
noradrenaline activity will be investigated. We will also look for
between-group differences.
Background summary
Noradrenaline (NA) is produced in the brain in the locus coeruleus (LC). NA
and its reuptake system, the noradrenaline transporter (NET), are implicated in
a wide range of cognitive functions, including attention, memory, and arousal.
As a result, the NA system is also of great interest in the context of
neurodegenerative disease such as Parkinson*s disease, Alzheimer*s disease, and
Alzheimer's dementia in Down syndrome, where such cognitive functions are
compromised. Recently, the identification of a suitable radiotracer for imaging
the NET using positron emission tomography (PET) has received growing
attention. The use of such a PET radiotracer enables the study of the NET
system in vivo. The most suitable of the currently available radiotracers is
[11C]methylreboxetine ([11C]MRB). [11C]MRB is being used worldwide in a growing
number of clinical studies.
Study objective
The aim of this study is to determine NET availability in patients with
neurodegenerative diseases to characterize NA system degeneration in people
with Alzheimer's disease, Parkinson's disease (with and without dementia) and
with Downsyndrome (with and without dementia). We hope that the results of this
study can help us develop a novel diagnostic tool and a starting point for
developing new therapeutic treatments.
Study design
This study will use PET imaging with the [11C]MRB radiotracer allowing in vivo
examination of NET availability in the locus coeruleus and key projection areas
(cortex, hippocampus). To be able to interpretate the PET data, MRI images of
the brain are needed. Furthermore we will perform a few assessments to
determine cogntive functioning and sleep behaviour (MMSE, NPI, PSQI, ADL and
iADL scales).
Study burden and risks
This study entails a minimum risk to the participants. In general, PET imaging
is a procedure with minimal adverse effects. Intravenous injection of the
tracer is minimally invasive. The concentration of the [11C]MRB tracer used in
this study does not have a pharmacological effect nor is it expected to cause
adverse effects. Participants do not directly benefit from the study. Outcomes
of this study will contribute to development of new diagnostic methods and
possibly therapeutic methods in the furture.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
all participants:
•age between 50 - 80 years
Healthy volunteers:
•Willingness to cooperate and sign written informed consent.
Participants with Alzheimer's disease:
•Diagnosis of AD according to the criteria from the National Institute on
Aging-Alzheimer*s Association (NIA-AA)
Willingness to cooperate and sign written informed consent.
•MMSE score between 18-26 (inclusive);
Participants with Parkinson's disease
• Willingness to cooperate and sign written informed consent.
•Diagnosis of PD according to the London Parkinson*s disease society brain
criteria
Participants with Parkinson's disease and dementia:
• Willingness to cooperate and sign written informed consent.
•Diagnosis of PD according to the London Parkinson*s disease society brain
criteria
• MMSE score between 18-26 (inclusive);
Participants with Down Syndrome:
•availability of a caregiver/proxy who will be present at visits.
Participants with Downsyndrome & dementia
•availability of a caregiver/proxy who will be present at visits.
•A Clinical diagnosis of AD based on the Dementia Scale for Down Syndrome
(Gedye A., 1995. Dementia Scale for Down Syndrome. Vancouver, BC: Gedye
Research and Consulting) and on the Behavioral and Pyschological Symptoms of
Dementia in Down Syndrome (BPSD-DS) scale (Dekker A.D. et al., 2018) developed
by our group and recently optimized (in press, Dekker A.D. et al., 2021).
Exclusion criteria
All participants:
•usage of any medication that affects the noradrenaline system
•Pregnancy
•Contra-indications for MRI or PET (such as claustrophobia)
• brain MRI evidence of any structural abnormality, such as major stroke or
mass that is likely to interfere with the interpretation of the PET scan;
•Past or present developmental disorder or psychiatric disorder (expect for
Down's syndrom)
Healthy volunteers:
• Abnormal results on the Mini-Mental State Examination (MMSE) (<27);
• (Subjective) memory complaints;
• Absence of signed informed consent form
Participants with Alzheimer's Disease:
• History of neurological conditions other than AD;
• Absence of signed informed consent form
Participants with Parkinson's disease
• History of neurological conditions other than PD;
• Absence of signed informed consent form
• Past or present developmental disorder or psychiatric disorder
Participants with Parkinson's disease and dementia:
• History of neurological conditions other than PD-D;
• Absence of signed informed consent form.
Participants with Down's Syndrome:
• Absence of signed informed consent form or of caretaker/study partner (proxy
consent and assent).
Participants with Down's syndrome & dementia
• Absence of signed informed consent form or of caretaker/study partner (proxy
consent and assent).
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 | EUCTR2021-002489-42-NL |
| CCMO | NL77767.042.21 |