Retinal FunctionRECOGNISEDNCT04281186
Retinal and Cognitive Dysfunction in Type 2 Diabetes
An observational study of Retinal Function and Cognitive Dysfunction, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
Trial summary
The retina shares similar embryologic origin, anatomical features and physiological properties with the brain and hence offers a unique and accessible "window" to study the correlates and consequences of subclinical pathology in patients with cognitive impairment. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Retinal Function, Cognitive Dysfunction, Microperimetry
- How many people
- 510 participants
- Where
- 1 siteSpain
- Study dates
- 16 Nov 2020to 31 Dec 2024
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: Subjects with type 2 diabetes, older than 65 years of age.
Who may be able to join
- Type 2 diabetes
- 65 years and older
- Diabetes duration of at least 5 years
- No overt retinopathy on fundus examination or fundus images, as determined by the evaluating ophthalmologist, in one or both eyes, and people with mild to moderate non-proliferative diabetic retinopathy (NPDR) as determined by the evaluating phthalmologists using fundus examination by slit-lamp biomicroscopy.
- Able to provide informed consent
- Prospective study:
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- In addition to the above, participants enrolled in the prospective longitudinal cohort study should fulfilled the following criteria:
- Diagnosis of MCI confirmed by a neuropsychological test battery (NTB) and a specialized physician. For the control group the absence of MCI will also be confirmed by a neuropsychological test battery (NTB) and a specialized physician.
- Diagnosis of no overt or mild to moderate NPDR (ETDRS DR level 20 to 47) confirmed by the reading centre.
Who cannot join
- Previous history of stroke or neurodegenerative diseases.
- Severe NPDR, Proliferative DR (PDR), Diabetic Macular Edema (DME) or other eye disorders affecting vision besides these complications of diabetic retinopathy (DR).
- Previous laser photocoagulation.
- Other diseases which may induce retinal neurodegeneration (e.g. glaucoma).
- Subjects with a refractive error ≥ ± 6 D.
- Media opacities that preclude retinal imaging.
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- HbA1C > 10% (86 mmol/mol).
- Severe systemic illness or personal circumstances that would not make it possible for patients to fulfil study protocols.
- Prospective study:
- In addition to the above, participants enrolled in the prospective longitudinal cohort study should fulfilled the following criteria:
- 1. Established dementia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Retinal and Cognitive Dysfunction in Type 2 Diabetes: Unraveling the Common Pathways and Identification of Patients at Risk of Dementia
The retina shares similar embryologic origin, anatomical features and physiological properties with the brain and hence offers a unique and accessible "window" to study the correlates and consequences of subclinical pathology in patients with cognitive impairment. Our hypothesis is that the neurodegeneration of the retina will run in parallel to the neurodegeneration of the brain and, therefore, the signs of neurodysfunction in the retinal assessment will be more evident in those patients with rapid cognitive decline. Microangiopathy will also participate in cognitive decline and its specific role, as well as usefulness of retinal imaging, will be also examined.
This is a multinational and multicentre cross-sectional study and prospective, longitudinal cohort observational study.
Read the detailed description
The study consists of two main parts: a cross-sectional part and a longitudinal part, aimed at a) to determine whether functional and/or structural retinal biomarkers or circulating biomarkers are able to differentiate people with mild cognitive impairment (MCI) within the type 2 diabetes (T2D) population (the investigators will be able to do in the cross-sectional study, and, thus, use retina and/or blood biomarkers as a potential proxy to events taking place in the brain); b)to determine whether functional and/or structural retinal biomarkers or circulating biomarkers can be used to determine the speed of cognitive decline in people with T2D and MCI and those at higher risk of developing dementia.
The cross-sectional study will allow characterization of a large group of individuals with T2D (720 participants) and establish correlations between the various functional and structural retinal endpoints obtained and the presence/absence of mild cognitive impairment (MCI) and dementia. The cross-sectional study will allow identification of T2D patients with MCI; of these a group of 168 T2D patients with MCI and a group of T2D patients without MCI (n=63), which will act as a control group, will be then followed prospectively in the longitudinal cohort study to evaluate end points predictive of cognitive decline and dementia.
The primary objective is: to assess whether retinal sensitivity measured by microperimetry is able to predict cognitive decline and progression to dementia in MCI T2D patients.
The secondary objectives are:
- To assess whether retinal sensitivity, measured by microperimetry, can identify individuals with MCI among people with T2D.
- To assess whether eye fixation, measured by microperimetry, can identify individuals with MCI among people with T2D.
- To assess whether eye fixation measured by microperimetry is able to predict rapid cognitive decline in T2D patients with MCI.
- To define a T2D phenotype at high risk of developing dementia based on retinal imaging and functional retinal assessments.
- To determine whether retinal imaging and functional retinal assessments may identify individuals with MCI among people with T2D.
- To define a T2D phenotype at high risk to develop cognitive decline and dementia based on retinal imaging plus brain imaging.
- To define a T2D phenotype at high risk to develop dementia based on retinal imaging plus brain imaging plus circulating biomarkers.
- To establish a score to predict cognitive decline or progression from MCI to dementia based on the variables included in the study.
- Conditions
- Retinal Function, Cognitive Dysfunction, Microperimetry
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cross-sectional cohort | Up to 720 type 2 diabetic patients (>5 years duration), older than 65 years of age are expected to be recruited in orfer to asure the sample of 168 patients with MCI and 63 normocognitive fulfilling criteria for the prospective study. | |
| Prospective study-MCI | Target 168 Patients from the cross-sectional cohort diagnosed with mild cognitive impairment during the cross-sectional evaluation | |
| Prospective study normocognitive | 63 Patients from the cross-sectional cohort without mild cognitive impairment evaluated during the cross-sectional evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retinal sensitivity
Assessed by microperimetry
Measured: 48 month
Secondary outcomes (12)
Retinal neurodysfunction/ neurodegeneration-1
Assessed by gaze fixation: areas BCEA63, BCEA95 and P1, P2 fixation points will be evaluated
Measured: 48 month
Retinal neurodysfunction/ neurodegeneration-2
Full-field photopic electroretinogram (ERG)
Measured: 48 month
Retinal neurodysfunction/ neurodegeneration-3
Spectral Domain Optical Coherence Tomography (SD-OCT): measurement of the retinal layers .
Measured: 48 month
Retinal vascular abnormalities-1
Assessed by Optical Coherence Tomography Angiography (OCT-A)
Measured: 48 month
Retinal vascular abnormalities-2
Ultra-wide field Fundus Fluorescein Angiography (FFA).
Measured: 48 month
Brain imaging-1
Assessed by Magnetic Resonance Imaging (MRI).
Measured: 48 month
Brain imaging-2
18 Fluoro-2-deoxyglucose-Positron Emission Tomography (18FDG-PET).
Measured: 48 month
Circulating biomarkers: Hypothesis free analysis
Blood samples: proteomics, complement system, inflammatory mediators, glial acidic fibrillary protein, HOMA-IR
Measured: 48 month
Geriatric Depression Scale
Geriatric Depression Scale (GDS-15): scores 0-4 normal, 5-8 mild depression, 9-11 moderate depression, 12-15 severe depression
Measured: 48 month
Quality of life: EQ-5D-3L
EQ-5D-3L questionnaire . The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Measured: 48 month
Visual Functioning Questionnaire
25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) . The NEI VFQ-25 contains a reduced number of items within each subscale of the original 51-item NEI VFQ. 13,29 The 12 subscales in the NEI VFQ-25 are general vision, near vision, distance vision, driving, peripheral vision, color vision, ocular pain, general health, and vision-specific role difficulties, dependency, social function, and mental health. The subscale scores are calculated by summing the relevant items and transforming the raw scores into a 0 to 100 scale where higher scores indicate better functioning or well-being. The total score of the NEI VFQ-25 is an average of 11 subscale scores, excluding the single-item general health subscale.
Measured: 48 month
Diabetes Specific Dementia Risk Score.
Diabetes Specific Dementia Risk Score (DSDRS). Briefly,the score is based on the age of the patients, history of any acute metabolic decompensation, the presence micro and/or macrovascular complications of the diabetes, depression and education level, obtaining a score ranged between -1 and 19. The higher the score, more risk of developing dementia at 10 years follow-up.
Measured: 48 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2020
- Study start16 Nov 2020
- Primary completion12 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinal FunctionStudies of the same condition, open and under way.
- More trials run by Hospital Universitari Vall d'Hebron Research InstituteThe 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
- Prospective
- Enrolment
- 510 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Queen's University, Belfast, Association for Innovation and Biomedical Research on Light and Image, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Rome Tor Vergata, Ospedale San Raffaele, University of Milan, University of Southern Denmark, Azienda Ospedaliero Universitaria Maggiore della Carita, Hospital Mutua de Terrassa, Institut Catala de Salut, University of Montenegro, Clinical Center of Montenegro, University of Cadiz, European Infrastructure for Translational Research, Alzheimer Europe, International Diabetes Federation Europe, Anaxomics Biotech S.L., Oxurion, Genesis Biomed
- Responsible party
- Principal investigator, Andreea Ciudin, Hospital Universitari Vall d'Hebron Research Institute
- Investigators
- Noemi Lois, Prof., Study director, Queen´s University BelfastRafael Simó, Prof, Study director, Vall Hebron Research Institute-VHIR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04281186
- Sponsor's protocol ID
- ECR-RET-2019-14
- Acronym
- RECOGNISED
- Status last verified
- Mar 2025
- First submitted
- 18 Feb 2020
- Last updated
- 12 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retinal and Cognitive Dysfunction in Type 2 Diabetes: Unraveling the Common Pathways and Identification of Patients at Risk of Dementia
- ClinicalTrials.gov ID
- NCT04281186
- Acronym / sponsor ID
- RECOGNISED / ECR-RET-2019-14
- Conditions
- Retinal Function, Cognitive Dysfunction, Microperimetry
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 510 participants (actual)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Collaborators
- Queen's University, Belfast, Association for Innovation and Biomedical Research on Light and Image, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Rome Tor Vergata, Ospedale San Raffaele, University of Milan, University of Southern Denmark, Azienda Ospedaliero Universitaria Maggiore della Carita, Hospital Mutua de Terrassa, Institut Catala de Salut, University of Montenegro, Clinical Center of Montenegro, University of Cadiz, European Infrastructure for Translational Research, Alzheimer Europe, International Diabetes Federation Europe, Anaxomics Biotech S.L., Oxurion, Genesis Biomed
- Study start
- 16 Nov 2020 (actual)
- Primary completion
- 12 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 24 Feb 2020 (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.
The retina shares similar embryologic origin, anatomical features and physiological properties with the brain and hence offers a unique and accessible "window" to study the correlates and consequences of subclinical pathology in patients with cognitive impairment. Our hypothesis is that the neurodegeneration of the retina will run in parallel to the neurodegeneration of the brain and, therefore, the signs of neurodysfunction in the retinal assessment will be more evident in those patients with rapid cognitive decline. Microangiopathy will also participate in cognitive decline and its specific role, as well as usefulness of retinal imaging, will be also examined.
This is a multinational and multicentre cross-sectional study and prospective, longitudinal cohort observational study.
Detailed description
The study consists of two main parts: a cross-sectional part and a longitudinal part, aimed at a) to determine whether functional and/or structural retinal biomarkers or circulating biomarkers are able to differentiate people with mild cognitive impairment (MCI) within the type 2 diabetes (T2D) population (the investigators will be able to do in the cross-sectional study, and, thus, use retina and/or blood biomarkers as a potential proxy to events taking place in the brain); b)to determine whether functional and/or structural retinal biomarkers or circulating biomarkers can be used to determine the speed of cognitive decline in people with T2D and MCI and those at higher risk of developing dementia.
The cross-sectional study will allow characterization of a large group of individuals with T2D (720 participants) and establish correlations between the various functional and structural retinal endpoints obtained and the presence/absence of mild cognitive impairment (MCI) and dementia. The cross-sectional study will allow identification of T2D patients with MCI; of these a group of 168 T2D patients with MCI and a group of T2D patients without MCI (n=63), which will act as a control group, will be then followed prospectively in the longitudinal cohort study to evaluate end points predictive of cognitive decline and dementia.
The primary objective is: to assess whether retinal sensitivity measured by microperimetry is able to predict cognitive decline and progression to dementia in MCI T2D patients.
The secondary objectives are:
- To assess whether retinal sensitivity, measured by microperimetry, can identify individuals with MCI among people with T2D.
- To assess whether eye fixation, measured by microperimetry, can identify individuals with MCI among people with T2D.
- To assess whether eye fixation measured by microperimetry is able to predict rapid cognitive decline in T2D patients with MCI.
- To define a T2D phenotype at high risk of developing dementia based on retinal imaging and functional retinal assessments.
- To determine whether retinal imaging and functional retinal assessments may identify individuals with MCI among people with T2D.
- To define a T2D phenotype at high risk to develop cognitive decline and dementia based on retinal imaging plus brain imaging.
- To define a T2D phenotype at high risk to develop dementia based on retinal imaging plus brain imaging plus circulating biomarkers.
- To establish a score to predict cognitive decline or progression from MCI to dementia based on the variables included in the study.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cross-sectional cohort | – | –Up to 720 type 2 diabetic patients (>5 years duration), older than 65 years of age are expected to be recruited in orfer to asure the sample of 168 patients with MCI and 63 normocognitive fulfilling criteria for the prospective study. |
| Prospective study-MCI | – | –Target 168 Patients from the cross-sectional cohort diagnosed with mild cognitive impairment during the cross-sectional evaluation |
| Prospective study normocognitive | – | –63 Patients from the cross-sectional cohort without mild cognitive impairment evaluated during the cross-sectional evaluation |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Subjects with type 2 diabetes, older than 65 years of age.
Key inclusion criteria (9 listed)
- Type 2 diabetes
- 65 years and older
- Diabetes duration of at least 5 years
- No overt retinopathy on fundus examination or fundus images, as determined by the evaluating ophthalmologist, in one or both eyes, and people with mild to moderate non-proliferative diabetic retinopathy (NPDR) as determined by the evaluating phthalmologists using fundus examination by slit-lamp biomicroscopy.
- Able to provide informed consent
Key exclusion criteria (11 listed)
- Previous history of stroke or neurodegenerative diseases.
- Severe NPDR, Proliferative DR (PDR), Diabetic Macular Edema (DME) or other eye disorders affecting vision besides these complications of diabetic retinopathy (DR).
- Previous laser photocoagulation.
- Other diseases which may induce retinal neurodegeneration (e.g. glaucoma).
- Subjects with a refractive error ≥ ± 6 D.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Retinal sensitivity
Time frame: 48 month
Assessed by microperimetry
12 secondary outcomes
Retinal neurodysfunction/ neurodegeneration-1
Time frame: 48 month
Retinal neurodysfunction/ neurodegeneration-2
Time frame: 48 month
Retinal neurodysfunction/ neurodegeneration-3
Time frame: 48 month
Retinal vascular abnormalities-1
Time frame: 48 month
Retinal vascular abnormalities-2
Time frame: 48 month
Brain imaging-1
Time frame: 48 month
Brain imaging-2
Time frame: 48 month
Circulating biomarkers: Hypothesis free analysis
Time frame: 48 month
Geriatric Depression Scale
Time frame: 48 month
Quality of life: EQ-5D-3L
Time frame: 48 month
Visual Functioning Questionnaire
Time frame: 48 month
Diabetes Specific Dementia Risk Score.
Time frame: 48 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
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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.
Noemi Lois, Prof. study director
Queen´s University Belfast
Rafael Simó, Prof study director
Vall Hebron Research Institute-VHIR
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 Retinal Function and Cognitive Dysfunction, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
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 9 inclusion and 11 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: finished, as of the sponsor's last update on 12 Mar 2025. 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 Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retinal sensitivity (time frame: 48 month). 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 12 Mar 2025.