Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy

NCT ID: NCT06582472

Last Updated: 2024-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-29

Study Completion Date

2025-05-19

Brief Summary

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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

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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.

Conditions

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Diabetic Retinopathy Diabetic Retinopathy Associated with Type 2 Diabetes Mellitus

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Ophthalmological examination including imaging assessments

Intervention Type PROCEDURE

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 cornea

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.

cohort 2 (longitudinal study)

healthy controls: subjects in good general health as evidenced by medical history without diagnosis of type 2 diabetes

Ophthalmological examination including imaging assessments

Intervention Type PROCEDURE

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 cornea

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.

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

Ophthalmological examination including imaging assessments

Intervention Type PROCEDURE

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 cornea

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.

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

Ophthalmological examination including imaging assessments

Intervention Type PROCEDURE

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 cornea

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

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 collection

Intervention Type PROCEDURE

collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.

Interventions

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Ophthalmological examination including imaging assessments

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)

Intervention Type PROCEDURE

confocal analysis of cornea

Confocal analysis of cornea: a procedure to study and quantify possible corneal nerve degeneration as a marker of involvement of diabetic neuropathy

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

tear sampling collection

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

Intervention Type PROCEDURE

blood sampling collection

collection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Participant is willing and able to give informed consent for participation in the trial.
2. Male or Female, aged 40 - 80 years;
3. 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;
4. HbA1c level 7% or greater;


1. Participant is willing and able to give informed consent for participation in the trial;
2. Male or Female, aged 40 - 80 years;
3. In good general health as evidenced by medical history without diagnosis of type 2 diabetes;


1. Participant is willing and able to give informed consent for participation in the trial;
2. Male or Female, aged 40 - 80 years;
3. 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;
4. HbA1c level 7% or greater.

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. retinal or systemic diseases other than diabetes;
2. hypertension (BP values greater than 140/90 mm Hg);
3. anemia (hematocrit less than 35%);
4. smoking;
5. laser treatment and pregnancy
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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IRCCS Ospedale San Raffaele

OTHER

Sponsor Role lead

Responsible Party

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Francesco Bandello

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Irccs Ospedale San Raffaele

Milan, Italy/milan, Italy

Site Status RECRUITING

IRCCS Ospedale San Raffaele _O.U. Ophthalmology

Milan, Italy, Italy

Site Status RECRUITING

Countries

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Italy

Facility Contacts

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Gianpaolo Zerbini, MD

Role: primary

+390226432148

Giulia Basile, MPharm

Role: primary

+39 0226433545

Other Identifiers

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PNRR-MAD-2022-12376008

Identifier Type: -

Identifier Source: org_study_id

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