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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT03821753

Collaborator

Délégation de la Recherche Clinique et de l'innovation (DRCI) (Other), CRC (Centre de Recherche Clinique) (Other), SFD (Société Francophone du Diabète) (Other)

120

Enrollment

Location

16.8

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Microvascular Complications Diabetic Retinopathy Diabetes Microangiopathy Angiography	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 Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Case-Control

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Jan 7, 2019

Anticipated Primary Completion Date :

May 1, 2020

Anticipated Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Macular capillary density in the external deep capillary network [3 months]
Macular capillary density in the external deep capillary network measured by OCT-Angiography (no later than 3 months after inclusion)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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