Diabetic Retinopathy2022-12376008NCT06582472
Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy
An observational study of Diabetic Retinopathy and Diabetic Retinopathy Associated with Type 2 Diabetes Mellitus, run by IRCCS Ospedale San Raffaele at 2 sites in Italy.
Trial summary
Despite the evidence that diabetic retinopathy (DR) remains the first cause of blindness among the working-age population, it lacks a specific preventive treatment. This is because early mechanisms leading to the development of DR have been, until recently, unknown. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetic Retinopathy, Diabetic Retinopathy Associated with Type 2 Diabetes Mellitus
- What is being tested?
- Ophthalmological examination including imaging assessments, confocal analysis of cornea and Dynamic Vessel Analyzer (DVA)
- Type of treatment
- Surgery or procedure
- How many people
- 180 participants
- Where
- 2 sitesItaly
- Study dates
- 29 Sep 2023to 19 May 2025
- How long will I take part?
- 24 Months
- 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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The longitudinal study will include 90 individuals affected by type 2 diabetes and 30 healthy controls. The cross-sectional study will include 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and no clinical signs of DR and 30 individuals (matched for age, gender and duration of diabetes) affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage (in absence of laser treatment).
Who may be able to join
- Participant is willing and able to give informed consent for participation in the trial.
- Male or Female, aged 40 - 80 years;
- In good general health as evidenced by medical history or diagnosed with type 2 diabetes for less than 10 years without clinical signs of retinopathy and other diabetic complications;
- HbA1c level 7% or greater;
- Participant is willing and able to give informed consent for participation in the trial;
- Male or Female, aged 40 - 80 years;
Show all 18Show fewer
- In good general health as evidenced by medical history without diagnosis of type 2 diabetes;
- Participant is willing and able to give informed consent for participation in the trial;
- Male or Female, aged 40 - 80 years;
- Patient with a diagnosis of type 2 diabetes for longer than 20 years in the absence or presence of clinical signs of retinopathy and other diabetic complications;
- HbA1c level 7% or greater.
- Exclusion Criteria (longitudinal study and cross-sectional study)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- retinal or systemic diseases other than diabetes;
- hypertension (BP values greater than 140/90 mm Hg);
- anemia (hematocrit less than 35%);
- smoking;
- laser treatment and pregnancy
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites, 2 recruiting
- Recruiting
Irccs Ospedale San Raffaele
Milan, Italy/milan, 20132
Gianpaolo Zerbini, MD, +390226432148, zerbini.gianpaolo@hsr.it
- Recruiting
IRCCS Ospedale San Raffaele _O.U. Ophthalmology
Milan, Italy, 20123
Giulia Basile, MPharm, +39 0226433545, basile.giulia@hsr.it
About this study
Despite the evidence that diabetic retinopathy (DR) remains the first cause of blindness among the working-age population, it lacks a specific preventive treatment. This is because early mechanisms leading to the development of DR have been, until recently, unknown. Recent studies have suggested that the early stages of DR could be preceded by neuronal abnormalities, in particular retinal ganglion cell death, coupled with widespread retinal inflammation. According to these studies, endothelial dysfunction and the development of microaneurysms, the classic hallmarks of DR, could be the consequence of these early abnormalities.
This project will aim to verify whether neurodegeneration could represent at the same time: 1) a risk factor for subsequent development of DR (this will be investigated through a follow-up study in type 2 diabetic patients free of diabetic retinopathy). 2) a biomarker of the complication (if so, patients with long-standing diabetes in the absence of retinopathy should show no signs of neurodegeneration).
Read the detailed description
The project is centered on a clinical study aimed to clarify whether early, diabetes-driven neurodegeneration (something that has been demonstrated by several seminal studies) is related (possibly causative) to the subsequent development of DR (a concept that is presently far from being confirmed but that, in case, would probably pave the way to identify for the first time a treatment for this diabetic complication.
This project includes two substudies:
- LONGITUDINAL STUDY: the aim is to verify whether the presence of retinal neurodegeneration in type 2 diabetic patients without DR increases the risk of subsequent development of retinal microaneurisms, the classic first vascular sign of DR; will enroll 90 individuals affected by type 2 diabetes and 30 healthy controls. All the subjects will be recruited during the first 6 months of the study and followed for 24 months (baseline, month 6, month 12, month 18, and month 24).
- CROSS-SECTIONAL STUDY: the aim is to verify the clinical evidence of retinal neurodegeneration in patients with type 2 diabetes diagnosed over 20 years and with overt diabetic retinopathy, compared to patients with type 2 diabetes diagnosed for over 20 years but no signs of diabetic retinopathy. Will be enrolled 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and no clinical signs of DR and 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage. All the subjects will be recruited during the first 6 months of the study and subjected to only one visit to the site.
- Being tested
- Ophthalmological examination including imaging assessments, confocal analysis of cornea, Dynamic Vessel Analyzer (DVA), tear sampling collection, blood sampling collection
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ophthalmological examination including imaging assessmentsProcedure or surgery
Ophthalmological examination including imaging assessments (SD-OCT, Spectral Domain Optical Coherence Tomography, a procedure to study and quantify possible retinal neurodegeneration and OCT-A, Optical coherence tomography angiography, a procedure to study and quantify possible retinal vascular abnormalities)
confocal analysis of corneaProcedure or surgery
Confocal analysis of cornea: a procedure to study and quantify possible corneal nerve degeneration as a marker of involvement of diabetic neuropathy
Dynamic Vessel Analyzer (DVA)Procedure or surgery
Dynamic Vessel Analyzer (DVA), a device that measures the response of retinal arteries and veins to a standardized stimulus (flickering light) allowing direct quantification of the inflammatory status of the retinal vasculature
tear sampling collectionProcedure or surgery
Collect and analyze tear samples to identify biomarkers in tears and at the endothelium of the ocular surface through impression conjunctival cytology and the quantitative/qualitative analysis of pro-inflammatory cytokines
blood sampling collectionProcedure or surgery
collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.
| Study group | Role | What they receive |
|---|---|---|
| cohort 1 (longitudinal study) | This group will include patients affected by type 2 diabetes for less than 10 years and without signs of diabetic retinopathy, nephropathy, and neuropathy. Receives: Procedure: Ophthalmological examination including imaging assessments; Procedure: confocal analysis of cornea; Procedure: Dynamic Vessel Analyzer (DVA); Procedure: tear sampling collection; Procedure: blood sampling collection | |
| cohort 2 (longitudinal study) | healthy controls: subjects in good general health as evidenced by medical history without diagnosis of type 2 diabetes Receives: Procedure: Ophthalmological examination including imaging assessments; Procedure: confocal analysis of cornea; Procedure: Dynamic Vessel Analyzer (DVA); Procedure: tear sampling collection; Procedure: blood sampling collection | |
| cohort 1 (cross sectional study) | Patients with a diagnosis of type 2 diabetes for longer than 20 years without clinical signs of retinopathy and other diabetic complications Receives: Procedure: Ophthalmological examination including imaging assessments; Procedure: confocal analysis of cornea; Procedure: Dynamic Vessel Analyzer (DVA); Procedure: tear sampling collection; Procedure: blood sampling collection | |
| cohort 2 (cross sectional study) | Patients with a diagnosis of type 2 diabetes for longer than 20 years with clinical signs of retinopathy and other diabetic complications Receives: Procedure: Ophthalmological examination including imaging assessments; Procedure: confocal analysis of cornea; Procedure: Dynamic Vessel Analyzer (DVA); Procedure: tear sampling collection; Procedure: blood sampling collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology
- Evaluation of changes in neuroretinal morphology by OCT (Optical coherence tomography), in the morphology of the retinal vascular component by OCT-A, and retinal blood perfusion due to the presence/absence of a light signal by Dynamic Vessel Analyzer);
- identification of retinal neurodegeneration factors as possible biomarkers of diabetic retinopathy, using conjunctival impression cytology and quantum/qualitative analysis of pro-inflammatory cytokines in tears and plasma;
- assessment of the appearance of signs of corneal nerve degeneration by confocal microscopy in patients with signs of overt retinal neurodegeneration.
Measured: 24 months
Secondary outcomes (1)
imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology
- Evaluation of changes in neuroretinal morphology by OCT (Optical coherence tomography), in the morphology of the retinal vascular component by OCT-A, and retinal blood perfusion due to the presence/absence of a light signal by Dynamic Vessel Analyzer);
- identification of retinal neurodegeneration factors as possible biomarkers of diabetic retinopathy, using conjunctival impression cytology and quantum/qualitative analysis of pro-inflammatory cytokines in tears and plasma;
- assessment of the appearance of signs of corneal nerve degeneration by confocal microscopy in patients with signs of overt retinal neurodegeneration.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start29 Sep 2023
- Primary completion19 May 2025 (estimated)
- Study completion19 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (estimated)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- IRCCS Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Bandello, IRCCS Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06582472
- Sponsor's protocol ID
- PNRR-MAD-2022-12376008
- Acronym
- 2022-12376008
- Status last verified
- Aug 2024
- First submitted
- 26 Aug 2024
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arrigo A, Aragona E, Zerbini G, Aragona P, Bandello F. Macular Pigment Changes in Patients with Diabetes Mellitus and Without Diabetic Retinopathy. Ophthalmol Ther. 2026 Aug 8. doi: 10.1007/s40123-026-01458-2. Online ahead of print.
PubMed 42570079
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy
- ClinicalTrials.gov ID
- NCT06582472
- Acronym / sponsor ID
- 2022-12376008 / PNRR-MAD-2022-12376008
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- IRCCS Ospedale San RaffaeleUniversity, hospital or other
- Study start
- 29 Sep 2023 (actual)
- Primary completion
- 19 May 2025 (estimated)
- Study completion
- 19 May 2025 (estimated)
- First posted
- 3 Sep 2024 (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.
Despite the evidence that diabetic retinopathy (DR) remains the first cause of blindness among the working-age population, it lacks a specific preventive treatment. This is because early mechanisms leading to the development of DR have been, until recently, unknown. Recent studies have suggested that the early stages of DR could be preceded by neuronal abnormalities, in particular retinal ganglion cell death, coupled with widespread retinal inflammation. According to these studies, endothelial dysfunction and the development of microaneurysms, the classic hallmarks of DR, could be the consequence of these early abnormalities.
This project will aim to verify whether neurodegeneration could represent at the same time: 1) a risk factor for subsequent development of DR (this will be investigated through a follow-up study in type 2 diabetic patients free of diabetic retinopathy). 2) a biomarker of the complication (if so, patients with long-standing diabetes in the absence of retinopathy should show no signs of neurodegeneration).
Detailed description
The project is centered on a clinical study aimed to clarify whether early, diabetes-driven neurodegeneration (something that has been demonstrated by several seminal studies) is related (possibly causative) to the subsequent development of DR (a concept that is presently far from being confirmed but that, in case, would probably pave the way to identify for the first time a treatment for this diabetic complication.
This project includes two substudies:
- LONGITUDINAL STUDY: the aim is to verify whether the presence of retinal neurodegeneration in type 2 diabetic patients without DR increases the risk of subsequent development of retinal microaneurisms, the classic first vascular sign of DR; will enroll 90 individuals affected by type 2 diabetes and 30 healthy controls. All the subjects will be recruited during the first 6 months of the study and followed for 24 months (baseline, month 6, month 12, month 18, and month 24).
- CROSS-SECTIONAL STUDY: the aim is to verify the clinical evidence of retinal neurodegeneration in patients with type 2 diabetes diagnosed over 20 years and with overt diabetic retinopathy, compared to patients with type 2 diabetes diagnosed for over 20 years but no signs of diabetic retinopathy. Will be enrolled 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and no clinical signs of DR and 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage. All the subjects will be recruited during the first 6 months of the study and subjected to only one visit to the site.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| cohort 1 (longitudinal study) | – | Procedure: Ophthalmological examination including imaging assessments, Procedure: confocal analysis of cornea, Procedure: Dynamic Vessel Analyzer (DVA), Procedure: tear sampling collection, Procedure: blood sampling collectionThis group will include patients affected by type 2 diabetes for less than 10 years and without signs of diabetic retinopathy, nephropathy, and neuropathy. |
| cohort 2 (longitudinal study) | – | Procedure: Ophthalmological examination including imaging assessments, Procedure: confocal analysis of cornea, Procedure: Dynamic Vessel Analyzer (DVA), Procedure: tear sampling collection, Procedure: blood sampling collectionhealthy controls: subjects in good general health as evidenced by medical history without diagnosis of type 2 diabetes |
| cohort 1 (cross sectional study) | – | Procedure: Ophthalmological examination including imaging assessments, Procedure: confocal analysis of cornea, Procedure: Dynamic Vessel Analyzer (DVA), Procedure: tear sampling collection, Procedure: blood sampling collectionPatients with a diagnosis of type 2 diabetes for longer than 20 years without clinical signs of retinopathy and other diabetic complications |
| cohort 2 (cross sectional study) | – | Procedure: Ophthalmological examination including imaging assessments, Procedure: confocal analysis of cornea, Procedure: Dynamic Vessel Analyzer (DVA), Procedure: tear sampling collection, Procedure: blood sampling collectionPatients with a diagnosis of type 2 diabetes for longer than 20 years with clinical signs of retinopathy and other diabetic complications |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The longitudinal study will include 90 individuals affected by type 2 diabetes and 30 healthy controls. The cross-sectional study will include 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and no clinical signs of DR and 30 individuals (matched for age, gender and duration of diabetes) affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage (in absence of laser treatment).
Key inclusion criteria (18 listed)
- Participant is willing and able to give informed consent for participation in the trial.
- Male or Female, aged 40 - 80 years;
- In good general health as evidenced by medical history or diagnosed with type 2 diabetes for less than 10 years without clinical signs of retinopathy and other diabetic complications;
- HbA1c level 7% or greater;
- Participant is willing and able to give informed consent for participation in the trial;
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Ophthalmological examination including imaging assessmentsOphthalmological examination including imaging assessments (SD-OCT, Spectral Domain Optical Coherence Tomography, a procedure to study and quantify possible retinal neurodegeneration and OCT-A, Optical coherence tomography angiography, a procedure to study and quantify possible retinal vascular abnormalities) | Procedure or surgery | cohort 1 (cross sectional study), cohort 1 (longitudinal study), cohort 2 (cross sectional study), cohort 2 (longitudinal study) |
| confocal analysis of corneaConfocal analysis of cornea: a procedure to study and quantify possible corneal nerve degeneration as a marker of involvement of diabetic neuropathy | Procedure or surgery | cohort 1 (cross sectional study), cohort 1 (longitudinal study), cohort 2 (cross sectional study), cohort 2 (longitudinal study) |
| Dynamic Vessel Analyzer (DVA)Dynamic Vessel Analyzer (DVA), a device that measures the response of retinal arteries and veins to a standardized stimulus (flickering light) allowing direct quantification of the inflammatory status of the retinal vasculature | Procedure or surgery | cohort 1 (cross sectional study), cohort 1 (longitudinal study), cohort 2 (cross sectional study), cohort 2 (longitudinal study) |
| tear sampling collectionCollect and analyze tear samples to identify biomarkers in tears and at the endothelium of the ocular surface through impression conjunctival cytology and the quantitative/qualitative analysis of pro-inflammatory cytokines | Procedure or surgery | cohort 1 (cross sectional study), cohort 1 (longitudinal study), cohort 2 (cross sectional study), cohort 2 (longitudinal study) |
| blood sampling collectioncollection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system. | Procedure or surgery | cohort 1 (cross sectional study), cohort 1 (longitudinal study), cohort 2 (cross sectional study), cohort 2 (longitudinal study) |
Primary outcome
imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology
Time frame: 24 months
* Evaluation of changes in neuroretinal morphology by OCT (Optical coherence tomography), in the morphology of the retinal vascular component by OCT-A, and retinal blood perfusion due to the presence/absence of a light signal by Dynamic Vessel Analyzer); * identification of retinal neurodegeneration factors as possible biomarkers of diabetic retinopathy, using conjunctival impression cytology and quantum/qualitative analysis of pro-inflammatory cytokines in tears and plasma; * assessment of the appearance of signs of corneal nerve degeneration by confocal microscopy in patients with signs of overt retinal neurodegeneration.
1 secondary outcome
imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Derived from this study: PubMed 42570079Arrigo A, Aragona E, Zerbini G, Aragona P, Bandello F. Macular Pigment Changes in Patients with Diabetes Mellitus and Without Diabetic Retinopathy. Ophthalmol Ther. 2026 Aug 8. doi: 10.1007/s40123-026-01458-2. Online ahead of print.
- Individual participant dataSharing planned: No
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetic Retinopathy and Diabetic Retinopathy Associated with Type 2 Diabetes Mellitus, run by IRCCS Ospedale San Raffaele at 2 sites in Italy.
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 18 inclusion and 0 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 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06582472, which also lists 1 linked publication.
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 3 Sep 2024.