Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04291144 |
| Other study ID # |
DLB-FEOBV |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2020 |
| Est. completion date |
March 1, 2023 |
Study information
| Verified date |
May 2022 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Lewy Body Dementia (DLB) is the second most common type of neurodegenerative dementia and
characterized by loss of cholinergic neurons in the cerebrum and possibly also internal
organs. A novel tracer, 18F-fluoroethoxybenzovesamicol (18F-FEOBV), binds to the cholinergic
vesicle transporter, a protein expressed uniquely in the vesicles of cholinergic
pre-synapses. Our aim is to investigate the cholinergic denervation in patients with DLB
using 18F-FEOBV. The investigators plan to recruit 30 patients with DLB and 20 healthy
controls to extensive cognitive assessment, computed and positron emission topography,
magnetic resonance imaging, and samples of blood. The investigators hypothesize that patients
with DLB, compared to controls, have decreased cholinergic innervation in cortical and
subcortical areas of the brain, intestines and heart, and that the denervation corresponds to
symptoms of autonomic and cognitive dysfunction.
Description:
Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia
after Alzheimer's disease. It is characterized by cognitive decline, cognitive fluctuations,
visual hallucinations, parkinsonism, and sleep disturbances. There is evidence of cholinergic
neuron loss in the cerebrum of DLB patients, and Lewy body pathology in the cholinergic
parasympathetic nerves of internal organs. A novel tracer, 18F-fluoroethoxybenzovesamicol
(18F-FEOBV), binds to the cholinergic vesicle transporter, a protein expressed uniquely in
the vesicles of cholinergic pre-synapses, and therefore a very specific marker for
cholinergic innervation. There is only one previous FEOBV publication in DLB (4 patients).
That study showed impressive imaging quality, far better than earlier cholinergic
PET-ligands, such as 11C-donepezil. Per Borghammer has pioneered the use of 11C-donepezil PET
to visualize cholinergic loss, and 18F-FEOBV PET represents the next generation of
high-resolution cholinergic imaging. The aim is to investigate the cholinergic denervation in
patients with DLB using 18F-FEOBV. The investigators hypothesize that, compared to healthy
elderly controls, patients with DLB show: (i) Cholinergic denervation in cortical and
subcortical structures of the brain, and in peripheral organs, specifically the gut,
pancreas, and heart. (ii) Correlations between cerebral cholinergic denervation and cognitive
decline, assessed with neuropsychometric measures. (iii) Correlations between cholinergic
denervation of internal organs and relevant symptoms of autonomic dysfunction, e.g.
orthostatic hypotension and constipation, and with objective measures of autonomic
malfunction, e.g. increased colonic transit time, increased intestinal volume, and reduced
heart rate variability. (iv) Thinning of the vagal nerve detected by ultra sound. (v)
Correlations between cerebral cholinergic denervation and perturbed neural networks measured
by functional MRI. Secondary aims are to compare the cerebral uptake of 18F-FEOBV in DLB
patients with/without markers of Alzheimer's Disease in the cerebrospinal fluid, relate the
pattern of glucose uptake (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose, 18F-FDG PET) to
that of 18F-FEOBV uptake in the cerebrum, and contribute to development of a diagnostic
alpha-synuclein assay.
The investigators plan to include 25-30 DLB patients and 20 matched healthy elderly controls.
Patients are recruited from the dementia clinic, Aarhus University. Inclusion criteria are
mild to moderate DLB, ability to give informed consent, and typical signs of DLB on an
18F-FDG-PET scan. Exclusion criteria are major psychiatric, neurologic and medical
comorbidities. The investigators will do a clinical assessment including full somatic and
neurological examinations, an extensive neuropsychological cognitive assessment, assess
autonomic symptoms and evaluate for sleep disorders, test for orthostatic hypotension and
heart rate variability and colonic transit time. The investigators will inject 300
megabecquerel (MBq) of 18F-FEOBV in a peripheral vein and scan the internal organs from 0-70
minutes. The patient then rests, and from 180-210 minutes post-injection, the brain is
imaged. This two-step method has been validated to give a robust estimate of the cholinergic
innervation of the brain. The investigators will also do magnetic resonance imaging of the
brain, ultrasound of vagal nerve, cerebrospinal fluid analysis and blood work. The
investigators plan to write a manuscript describing the cerebral uptake of 18F-FEOBV as
measure of cholinergic denervation of patients with DLB. A second manuscript will describe
the uptake of 18F-FEOBV in the internal organs. A third manuscript will compare the
cholinergic denervation of brain and organs to cognitive and autonomic symptoms. NO will
participate in recruitment of patients, drafting of protocol and manuscripts, organizing
logistics, analysis of data, and collecting clinical and paraclinical data. The investigators
will pay particular attention the ethical issues of obtaining informed consent from demented
persons and emphasize an evaluation of competence. The investigators expect that this method
is better than the currently used 11C-donepezil, in which case it will replace its use for
studies of cholinergic denervation in the future. Developing non-invasive PET imaging of
short duration is particularly important in a demented patient population that often struggle
to lie still during prolonged scanning sessions. Development of strong objective measures to
aid diagnosis of DLB is important because DLB is a common disease projected to increase even
further in prevalence in the years to come. Also, our side project of contributing to the
development of a prion-assay to detect alpha-synuclein in the cerebrospinal fluid has
promising clinical potential.
