The Effect of the Glycemic Variability on Macular Retinal Microcirculation and Cognitive Functions in Patient With Type 1 Diabetes (REVADIAB)

Revadiab is case-control study aimed to demonstrate that retinal capillary density is altered in patients with type 1 diabetes with glycemic variability compared to those with comparable glycemic control without glycemic variability. An OCT angiography will be used to precisely evaluate retinal capillary density.

A secondary objective will be to evaluate if glycemic variability is associated with cognitive dysfunction, using a neuro psychologic evaluation.

Study Overview

• Status: Unknown
• Conditions: Diabetes; Diabetic Retinopathy; Microangiopathy; Angiography; Microvascular Complications
• Intervention / Treatment: Other: Case; Other: Control

Detailed Description

HbA1c doesn't explain all the microvascular complications of diabetes, especially microvascular complications. Glycemic variability is associated with increased oxidative stress, free radicals and endothelial dysfunction; it contributes to the pathogenesis of diabetic complications.

The relationship between glycemic variability and microangiopathic complications especially retinal but also neurological, needs to be studied.

The principal objective of Revadiab study is to demonstrate a correlation between glycemic variability and macular retinal microcirculation in patient with type 1 diabetes.

The secondary objective is to search a correlation between glycemic variability and :

• Alteration of cognitive functions.
• Severity of peripheral diabetic retinopathy and retinal neuronal damage.
• Other micro and macro angiopathic complications.
• Oxidative stress and inflammation.

Two groups of type 1 diabetic patients will be compared:

• Case: Patient with significant glycemic variability.
• Control: Patients without glycemic variability.

The severity of diabetic retinopathy will be evaluated by the degree of occlusion of small vessels in the central retinal region as measured by OCT angiography.

Acts or Product necessary to research :

• Non-invasive retinal imaging (OCT and OCT- Angiography, retinophotography)
• Neuropsychological tests.
• Blood test.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Jean Pierre RIVELINE, Professor; Phone Number: +33(0) 1 49 95 83 79; Email: jeanpierre.riveline@aphp.fr

Study Locations

• France
  • Ile-de-France
    • Paris, Ile-de-France, France, 75475
      • Recruiting
      • Hopital Lariboisiere
      • Contact: Jean-Pierre RIVELINE, Professor; Phone Number: +33(0) 1 49 95 83 79; Email: jeanpierre.riveline@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Inclusion of adult patients with T1D with more than 10 years of diabetes and users of the FreeStyle Free continuous measurement system.

Case: Patients with glycemic variability, defined by a coefficient of variation (CV) > 36%, calculated from continuous glucose measurements data by Free Style Libre® (Abbott).

Controls: Patients without glycemic variability, defined by a coefficient of variation (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for HbA1c (+/- 0.5%).

Description

Inclusion Criteria:

• Patients ≥ 18 years
• Type 1 diabetes (T1D)
• Using Free FreeStyle
• Diabete evolving for 10 years or more
• Case: Patients with glycemic variability, defined by a coefficient of variation (CV) > 36%, calculated from continuous glucose measurements data by Free Style Libre® (Abbott)
• Controls: Patients without glycemic variability, defined by a coefficient of variation (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for HbA1c (+/- 0.5%)

Exclusion Criteria:

• Type 2 diabetic patient
• Corticotherapy
• Comorbidity like cancer
• Antecedent of vitreoretinal pathology
• Antecedent of vitreoretinal surgery
• Important cataract, with an important opacity that prevents a reliable evaluation of capillary density in OCT angio
• Pregnant or lactating woman

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; Patients with glycemic variability, defined by a coefficient of variation (CV)> 36%, calculated from continuous glucose measurements data by Free Style Libre® (Abbott)	Other: Case; OCT; OCT-Angiography,; Retinophotography; Neuropsychological tests
Control; Patients without glycemic variability, defined by a coefficient of variation (CV) ≤ 36%, calculated from Free Style Libre® data and matched to patients in the Case group for HbA1c (+/- 0.5%)	Other: Control; OCT; OCT-Angiography,; Retinophotography; Neuropsychological tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Macular capillary density in the external deep capillary network	Macular capillary density in the external deep capillary network measured by OCT-Angiography (no later than 3 months after inclusion)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Macular capillary density in the deep capillary and deep capillary network	Macular capillary density in the deep capillary and deep capillary network measured by OCT-angiography (no later than 3 months after inclusion)	3 months
Area of the central avascular zone	Area of the central avascular zone by OCT-Angiography (no later than 3 months after inclusion)	3 months
Macular edema presence	Macular edema presence by OCT (no later than 3 months after inclusion)	3 months
Layer thickness reduction of the ganglion cells	Layer thickness reduction of the ganglion cells measured by OCT (no later than 3 months after inclusion)	3 months
Diabetic retinopathy stage	Diabetic retinopathy stage evaluated with retinographies (no later than 3 months after inclusion)	3 months
Development of pre-retinal neovascular vessels and/or pre-papillary	Development of pre-retinal neovascular vessels and/or pre-papillary (no later than 3 months after inclusion)	3 months
Occurrence of neovascular complications	Occurrence of neovascular complications: vitreous	3 months
Haemorrhage, retina tractional detachment, neovascular glaucoma	Haemorrhage, retina tractional detachment, neovascular glaucoma (no later than 3 months after inclusion)	3 months
Renal function evaluation	Renal function evaluation: microalbuminuria and creatinine determination (no later than 3 months after inclusion)	3 months
Evaluation of peripheral neuropathy	Evaluation of peripheral neuropathy : monofilament test (no later than 3 months after inclusion)	3 months
Ischemic cardiopathy	Measurement method: treatment with angioplasty or coronary artery bypass graft, Assessment of vascular risk by measuring the coronal calcium score, and determination of BNP and troponin. (no later than 3 months after inclusion)	3 months
Number of severe hypoglycemia	Number of severe hypoglycemia since 1 year, threshold for hypoglycemia no later than 3 months after inclusion)	3 months
Markers of inflammation	characterization of circulating inflammatory and endothelial cells and CRP-US assay	3 months
Oxidative stress markers	Oxidative stress markers: Measurements of 8-iso-prostaglandin F2 alpha urinary and 1,5-anhydroglucitol sanguine. (no later than 3 months after inclusion)	3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Délégation de la Recherche Clinique et de l'innovation (DRCI); CRC (Centre de Recherche Clinique); SFD (Société Francophone du Diabète)

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Diabetic retinopathy; Glycemic variability; Microangiopathy; Cognitive dysfunction; Macular retinal microcirculation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: K170406J

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