Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03466177 |
| Other study ID # |
S60932 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2018 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
October 2023 |
| Source |
Universitaire Ziekenhuizen KU Leuven |
| Contact |
Jan Van Eijgen, MD |
| Phone |
+3216332387 |
| Email |
jan.1.vaneijgen[@]uzleuven.be |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Because of a shared ontogenic origin, the retina displays similarities to the brain and
spinal cord in terms of anatomy, functionality, response to insult, and immunology. Hence,
the retina can be approached as an integral part of the central nervous system. The occurence
of ocular manifestations in several neurodegenerative pathologies, such as Alzheimer's
disease and Parkinson's disease, accentuates the strong relationship between eye and brain.
Particularly retinal changes can present a substrate for cerebral changes in these disorders.
Offering a 'window to the brain', the transparent eye enables non-invasive imaging of these
changes in retinal structure and vasculature. In this project, the potential of retinal
biomarkers for e.g. Alzheimer's will be explored with the aim to overcome some of the hurdles
in the current management of these pathologies, mainly the lack of techniques for patient
screening and early diagnosis. The aim of this clinical trial is to correlate the retinal
biomarkers for Alzheimer's with neuro-imaging, and cognitive function. Integrating the
results will yield non-invasive retinal biomarkers for clinical research, screening, and
follow-up of disease progression in various neurodegenerative disorders.
Description:
Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause
of dementia worldwide. A growing number of people are surviving into their 80s-90s and the
number of AD patients projected to nearly triple in the next three decades, affecting 80-90
million people worldwide by 2040. As such, AD will become the third cause of death for older
people, just behind cardiovascular disease and cancer. In contrast to the latter, AD cannot
be prevented, slowed or cured. AD represents an enormous socio-economic burden and has become
a trillion dollar disease. Despite decades of intensive research, diagnosis and treatment
remain challenging for AD. A string of recent failures in clinical trials for AD drugs has
pointed out that our understanding of the disease is still far from complete. More in detail,
three major reasons underlying this treatment gap have been identified:
i. The lack of techniques for patient screening and early diagnosis. ii. The incomplete
understanding of the complex interplay of pathological processes that underlie AD.
iii. The many hurdles between drug discovery and approval.
With this study, the investigators propose a novel way to address these needs, by using the
retina as a model organ to study the central nervous system (CNS). Many of the hallmark
cerebral pathophysiological processes of AD have also been observed in the retina. Unlike the
rest of the CNS, the retina can be visualized directly, with an imaging resolution up to 100x
higher than PET and MRI scans. Using these high-resolution imaging tools such as Optical
Coherence Tomography (OCT), studies have demonstrated microvascular changes and neuro-retinal
thinning in AD patients. Pilot data show that retinal Aβ can be visualized non-invasively
solely based on the intrinsic hyperspectral signature of aggregated amyloid deposits.
Non-invasive retinal imaging (e.g., fundus photography, OCT, hyperspectral imaging (HSI)) -
which are all available at affordable cost -, could therefore represent novel means for
identifying patients at risk, for longitudinal follow-up of disease progression in AD
patients, and for research in a quest for more effective treatments.
This is an open-label longitudinal biomarker study without investigational medicinal product
in subjects in different stages of the AD spectrum.
The data that we will collect consist of amyloid imaging, MRI, blood, genetic, general health
and cognitive data, as well as visual acuity, ocular biomicroscopy and funduscopy, fundus
photographs, hyperspectral retinal images, Optical Coherence Tomography (OCT) retinal images
and OCT angiography (OCT-A) retinal images. Subjects will be followed longitudinally. In the
current study the investigators will primarily investigate the potential of non-invasive,
multimodal retinal imaging for the early detection of Alzheimer's disease and for the
evaluation of disease progression. This will be done in comparison with amyloid imaging and
neuropsychological evaluations.
The investigators will build a longitudinal database of ocular, systemic, neuro-psychiatric,
MRI and PET imaging parameters of Aβ-positive and Aβ-negative patients with different stages
of cognitive impairment. This database will be used to provide proof-of-concept that retinal
biomarkers provide an early, accurate and non-invasive tool for AD detection and follow-up.
All data will be collected in a database for statistical analysis.
