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Optical Coherence Tomography in Cerebral Amyloidosis

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ClinicalTrials.gov Identifier: NCT03472482
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : March 21, 2018
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

In this observational study, the investigators aim to evaluate whether changes in the retinal and choroidal circulation, as assessed by Optical Coherence Tomography (OCT) and the quantification of retinal amyloid deposits using auto-fluorescence and hyperspectral retinal imaging, are correlated with the degree and subtype of dementia and with the presence or absence of a positive amyloid scan.

For this purpose, patients with established Alzheimer's Disease (AD) and Lewy Body Dementia (LBD), as well as amyloid positive and amyloid negative Mild Cognitive Impairment (MCI) and aged matched cognitively intact patients will be included in this cross-sectional study.


Condition or disease Intervention/treatment
Alzheimer Disease Dementia Alzheimers Dementia Lewy Body Disease Dementia, Lewy Body Mild Cognitive Impairment Diagnostic Test: non-invasive retinal imaging

Detailed Description:

Being a direct extension of the central nervous system and the only place in the human body where the vessels of the central circulation can be visualized directly, the eye provides a unique window to investigate the central circulatory system. Several studies have demonstrated that retinal blood vessels show structural and functional alterations in patients with dementia. These measurements are based on fundus pictures and are hence limited to the larger retinal vessels.

Until recently, intravenous injection of a contrast agent was necessary to visualize the retinal microvasculature in detail. While indispensable for the diagnosis of some ocular vascular diseases (arterial/venous occlusion, neovascularization,…) the invasiveness of fluorescein angiography (and the risk of an allergic reaction) limits its use as a screening tool to detect alterations in the microvascular network of the retina and choroid.

Optical coherence tomography (OCT) is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood. Since OCT is fast, easy to perform and completely non-invasive, this technique lends itself for screening purposes.

Auto-fluorescence retinal imaging is an imaging modality that is commonly used in ophthalmological practice to assess retinal pigment epithelium and photoreceptor function by quantifying the relative amount of auto-fluorescent lipofuscin. The images can be acquired using the OCT device but require pupil dilation. Using visible light of 488nm, it is a safe imaging technique with no short or late term side-effects to the patient. A recent study has described abnormal auto-fluorescence patterns in patients with cerebral amyloid deposition.

Hyperspectral fundus photography is comparable to regular fundus photography but uses an image sensor that can acquire images at multiple different wavelengths (unlike the classical red-green-blue colour sensors that are used in conventional cameras). Apart from a different image sensor, the device is identical to a regular fundus camera. Recent studies have emerged that describe a unique hyperspectral signature of aggregated retinal amyloid deposits.

The proposed study aims to investigate whether retinal or choroidal vascular parameters measured using OCT and the quantification of retinal amyloid deposits using auto-fluorescence and hyperspectral retinal imaging, could be useful to identify different subpopulations of cognitive intact, MCI and dementia patients.


Study Type : Observational [Patient Registry]
Estimated Enrollment : 85 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 1 Day
Official Title: Optical Coherence Tomography in Cerebral Amyloidosis
Actual Study Start Date : March 25, 2016
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2019


Group/Cohort Intervention/treatment
Ab+ cognitively intact volunteers

amyloid-positive cognitively intact controls (55-80 years)

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging
Ab- cognitively intact volunteers

amyloid-negative cognitively intact controls (55-80 years)

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging
amyloid-positive MCI patients

amyloid-positive patients with Mild Cognitive Impairment

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging
amyloid-negative MCI patients

amyloid-negative patients with Mild Cognitive Impairment

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging
AD patients

patients in the dementia stage of Alzheimer's Disease

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging
LBD patients

patients with Lewy Body Dementia

interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging

Diagnostic Test: non-invasive retinal imaging



Primary Outcome Measures :
  1. Diagnostic performance of OCT measurements in dementia [ Time Frame: 2 years ]
    area under the curve (AUC) on receiver operating characteristic curves



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Cfr. Eligibility Criteria
Criteria

Inclusion Criteria:

  • Cognitively intact healthy controls will be recruited from an ongoing community-recruited longitudinal cohort of cognitively intact older adults (55-85 years, S51125) who all have undergone amyloid Positron Emission Tomography (PET) at the baseline visit in the context of study S51125. Half of the subjects will be amyloid-positive and half will be amyloid-negative. In the context of study S51125 these subjects receive two-yearly neuropsychological assessment.
  • MCI patients (Petersen et al., 2004 criteria) will be recruited from an ongoing memory-clinic recruited longitudinal cohort of patients with amnestic mild cognitive impairment who participate in study S55892. All subjects have undergone an amyloid PET at the baseline study in the context of study S55892. Half of the subjects will be amyloid-positive and half will be amyloid negative.
  • Clinically probable AD subjects (National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria) will be recruited from the memory clinic University Hospitals Leuven (MMSE 12-28). Subjects will be recruited only if they are capable of providing written informed consent.
  • Clinically probable LBD (McKeith et al. criteria, 2005) will be recruited from the memory clinic University Hospitals Leuven (MMSE 12-28). Subjects will be recruited only if they are capable of providing written informed consent.
  • Capable and willing to participate

Exclusion Criteria:

  • Personal medical history of retinal neovascularization
  • Unable or unwilling to give consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472482


Contacts
Contact: Karel Van Keer, MD +3216332387 karel.vankeer@uzleuven.be

Locations
Belgium
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Karel Van Keer, MD    +3216332387    karel.vankeer@uzleuven.be   
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
Principal Investigator: Evelien Vandewalle, MD PhD UZ Leuven/KU Leuven
  Study Documents (Full-Text)

Documents provided by Universitaire Ziekenhuizen Leuven:
Study Protocol  [PDF] April 17, 2016


Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT03472482     History of Changes
Other Study ID Numbers: S59048
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Universitaire Ziekenhuizen Leuven:
Alzheimer's disease
Dementia
Lewy body disease
Retina
Retinal imaging
Optical Coherence Tomography
Hyperspectral imaging
Mild Cognitive Impairment

Additional relevant MeSH terms:
Lewy Body Disease
Alzheimer Disease
Dementia
Cognitive Dysfunction
Amyloidosis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Proteostasis Deficiencies
Metabolic Diseases
Parkinsonian Disorders
Basal Ganglia Diseases
Movement Disorders