Clinical trial NCT02671864: Incretin-mimetic Hypoglycemic Drugs and Severe Retinopathy
Official title: Impact of Incretin-mimetic Hypoglycaemic Drugs on Diabetic Retinopathy in Type 2 Diabetic Patients and Study of Biomarkers in the Development of Severe Retinopathy: Angiosafe-T2D Study 2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 2 Diabetes
Keywords: Incretin-based therapy
GLP1
Angiogenesis Inflammation
Hypoglycaemic treatment
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Assistance Publique Hopitaux De Marseille
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Centre National de la Recherche Scientifique, France
name: Collège de France
name: University of Paris 5 - Rene Descartes
name: Pierre and Marie Curie University
name: University Paris 7 - Denis Diderot
name: Aix Marseille Université
First posted: 2016-02-02
Enrollment: 7200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Experimental data suggest that GLP-1 promote endothelial cell growth and angiogenesis which may have beneficial effects on the cardiovascular system but harmful effects on the retina . This project investigate the possible link between incretin therapy and Severe Diabetic Retinopathy. The prevalence of severe DR in patients exposed to incretin therapy (GLP-1 analogs or DPP4 inhibitors) is compared to that in non-exposed patients to these antidiabetic classes.

Detailed description: This study is dedicated to investigate the impact of routinely prescribed hypoglycaemic treatments on the prevalence of severe retinopathy and to seek possible biomarkers of severe retinopathy. Hypoglycemic treatments taken by the patients are those prescribe by the usuel diabetogist in the context of routine care.

The study includes T2D patients according to ADA criteria treated with any kind of hypoglycemic treatment and attending a diabetes center (three in Marseille: Department of Endocrinology, Hôpital Nord, Assistance Publique des Hôpitaux de Marseille and Service d'Ophtalmologie, Hôpital Saint-Joseph and Service de Diabétologie, Hôpital Saint-Joseph, and two in Paris : Centre Universitaire du Diabète et de ses Complications Hôpital Lariboisière, Université Paris 7, Assistance Publique des Hôpitaux de Paris and Service d'Endocrinologie, Diabétologie et Nutrition, Hôpital Bichat).

It consists of two visits: Visits1 "Inclusion" and Visits 2 "three years after the inclusion". In each visit, the investigators will collect results of eye examination (fundus) and annual diabetes check up including anthropometric data, routine biology, diabetes complication status as well as medications taken by the patients (past and current). A bio-banking (blood, urine and hairs) will be also collected. Primary objective : to compare the prevalence of severe DR in patients exposed to incretin therapy (GLP-1 analogs or DPP4 inhibitors) to that in non-exposed patients at baseline.

Secondary objective: To compare the proportion of patients who worsen DR between V1 (inclusion) and V2 (after 3-yr of treatment) in patients exposed to incretin-based therapy from baseline vs non-exposed patients: patients with no DR or mild to moderate non proliferative DR at V1 who progress to severe DR at V2.

To evaluate whether the concentrations of angiogenic/inflammatory molecules and circulating endothelial and inflammatory cells are associated with severe DR in relation with the use of GLP-1 based therapy at V1 and V2.

Eligibility criteria: Inclusion Criteria:

* T2D patients according to ADA criteria treated with any kind of hypoglycaemic treatment
* Age above 18 years

Exclusion Criteria:

* Type 1 diabetes
* Patients with cataract preventing DR grading
* Patients who had panretinal photocoagulation more than 10 years ago
* Documented pregnancy or lactation

Primary outcomes:
measure: Prevalence of Severe DR at V1 (inclusion)
timeFrame: at inclusion
Secondary outcomes:
measure: Prevalence of severe DR at V2 (after 3 years of treatment)
timeFrame: after 3 years
measure: Plasma concentrations of ANGPT4
timeFrame: at inclusion and 3 years
measure: Plasma concentrations of VEGF
timeFrame: at inclusion and 3 years
measure: Plasma concentrations of proinflammatory cytokines such as IL-1beta, IL-6, IL-8, TNF-alpha
timeFrame: at inclusion and 3 years
measure: Concentrations of blood circulating EPCs and PBMCs
timeFrame: at inclusion and 3 years
Other outcomes:
Locations:
city: Marseille
country: France
facility: Hôpital de la Conception
city: Paris
country: France
facility: Département de Diabétologie - Hopital Lariboisière
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: GAUTIER Jean-François, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaborit B, Julla JB, Besbes S, Proust M, Vincentelli C, Alos B, Ancel P, Alzaid F, Garcia R, Mailly P, Sabatier F, Righini M, Gascon P, Matonti F, Houssays M, Goumidi L, Vignaud L, Guillonneau X, Erginay A, Dupas B, Marie-Louise J, Autie M, Vidal-Trecan T, Riveline JP, Venteclef N, Massin P, Muller L, Dutour A, Gautier JF, Germain S. Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz069. doi: 10.1210/clinem/dgz069.