Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy (2022-12376008)

August 30, 2024 updated by: Francesco Bandello, IRCCS Ospedale San Raffaele

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).

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

180

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

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).

Description

Inclusion Criteria - Longitudinal study (patients):

  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;

Inclusion Criteria - Longitudinal study (healthy controls)

  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;

Inclusion Criteria - Cross-sectional study

  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 (longitudinal study and cross-sectional study)

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Ospedale San Raffaele

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2023

Primary Completion (Estimated)

May 19, 2025

Study Completion (Estimated)

May 19, 2025

Study Registration Dates

First Submitted

August 26, 2024

First Submitted That Met QC Criteria

August 30, 2024

First Posted (Actual)

September 3, 2024

Study Record Updates

Last Update Posted (Actual)

September 3, 2024

Last Update Submitted That Met QC Criteria

August 30, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PNRR-MAD-2022-12376008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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