Alzheimer DiseaseNCT03472482
Optical Coherence Tomography in Cerebral Amyloidosis
An observational study of Alzheimer Disease and Dementia Alzheimers, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Dementia Alzheimers, Dementia
- What is being tested?
- non-invasive retinal imaging
- How many people
- 85 participants
- Where
- 1 siteBelgium
- Study dates
- 25 Mar 2016to 31 Dec 2019
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Cfr. Eligibility Criteria
Who may be able to join
- 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
Who cannot join
- Personal medical history of retinal neovascularization
- Unable or unwilling to give consent
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
UZ Leuven
Leuven, 3000
Karel Van Keer, MD, +3216332387, karel.vankeer@uzleuven.be
About this study
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.
Read the 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.
- Conditions
- Alzheimer Disease, Dementia Alzheimers, Dementia, Lewy Body Disease, Dementia, Lewy Body, Mild Cognitive Impairment
- Being tested
- non-invasive retinal imaging
- Keywords
- Alzheimer's disease, Dementia, Lewy body disease, Retina, Retinal imaging, Optical Coherence Tomography, Hyperspectral imaging, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Dementia, Lewy Body Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-invasive retinal imagingDiagnostic test
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Diagnostic Test: non-invasive retinal imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance of OCT measurements in dementia
area under the curve (AUC) on receiver operating characteristic curves
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2018
- Study start25 Mar 2016
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 85 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Evelien Vandewalle, MD PhD, Principal investigator, UZ Leuven/KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03472482
- Sponsor's protocol ID
- S59048
- Status last verified
- Jan 2018
- First submitted
- 19 Jan 2018
- Last updated
- 21 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optical Coherence Tomography in Cerebral Amyloidosis
- ClinicalTrials.gov ID
- NCT03472482
- Acronym / sponsor ID
- S59048
- Conditions
- Alzheimer Disease, Dementia Alzheimers, Dementia, Lewy Body Disease, Dementia, Lewy Body, Mild Cognitive Impairment
- Keywords
- Alzheimer's disease, Dementia, Lewy body disease, Retina, Retinal imaging, Optical Coherence Tomography, Hyperspectral imaging, Mild Cognitive Impairment
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 25 Mar 2016 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 21 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Ab+ cognitively intact volunteers | – | Diagnostic Test: non-invasive retinal imagingamyloid-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 |
| Ab- cognitively intact volunteers | – | Diagnostic Test: non-invasive retinal imagingamyloid-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 |
| amyloid-positive MCI patients | – | Diagnostic Test: non-invasive retinal imagingamyloid-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 |
| amyloid-negative MCI patients | – | Diagnostic Test: non-invasive retinal imagingamyloid-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 |
| AD patients | – | Diagnostic Test: non-invasive retinal imagingpatients 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 |
| LBD patients | – | Diagnostic Test: non-invasive retinal imagingpatients with Lewy Body Dementia interventions: non-invasive retinal imaging with Optical Coherence Tomography (OCT), OCT-angiography (OCT-A), Autofluorescence, Fundus Photography, Hyperspectral Imaging |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Cfr. Eligibility Criteria
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- Personal medical history of retinal neovascularization
- Unable or unwilling to give consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| non-invasive retinal imaging | Diagnostic test | AD patients, Ab+ cognitively intact volunteers, Ab- cognitively intact volunteers, LBD patients, amyloid-negative MCI patients, amyloid-positive MCI patients |
Primary outcome
Diagnostic performance of OCT measurements in dementia
Time frame: 2 years
area under the curve (AUC) on receiver operating characteristic curves
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evelien Vandewalle, MD PhD principal investigator
UZ Leuven/KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease and Dementia Alzheimers, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karel Van Keer, MD (+3216332387, karel.vankeer@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance of OCT measurements in dementia (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2018.