Endothelial Dysfunction and Diabetes (DENDI)

Assessment of Endothelial Dysfunction in Retinal and Peripheral Retinal Vessels in Diabetes

The aim of the study is to progress in the understanding of the early retinal vascular and neural abnormalities in patients with diabetes, using a new device, the Dynamic Vessel Analyzer. The Dynamic Vessel Analyzer allows to measure the diameter of the retinal vessels and to assess how it varies in presence of various stimuli. Then, we will be able to assess if a vascular and/or a neural dysfunction is present early in patient with diabetes.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Trinitrin; Drug: Neosynephrine 10% collyrium; Drug: Iontophoresis with acetylcholine delivery; Device: Dynamic Vessel Analyzer

Detailed Description

Twenty patients with type 1 diabetes without diabetic retinopathy and without arterial hypertension will be compared with 20 sex and aged-matched healthy control subjects. To assess the presence of retinal endothelial dysfunction, the variations of the diameters of the retinal vessels will be assessed using the Dynamic Vessel Analyzer, before and after flicker light stimulation, sublingual nitroglycerin, neosynephrine eyedrops, and isometric contraction. To assess the presence of peripheral endothelial dysfunction, the microcirculation of the forearm skin will be studied using iontophoresis with acetylcholine delivery, and heat delivery, both coupled with blood flow measurement using laser Doppler. An intravital capillaroscopy of the phalanx skin will be performed. The serum levels of CRP, ICAM-1, VCAM-1, VEGF, angiopoietin 2 and endostatin will also be measured.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hôpital LARIBOISIERE Service d'Ophtalmologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 1 diabetes: Diabetes duration >= 5 years, age >= 18 and <= 60 years old, patients with no visible diabetic retinopathy, and no arterial hypertension

Healthy subjects: Sex and age-matched control healthy subjects

Description

Inclusion Criteria:

• For diabetic patients :

  • age between 20 and 60
  • type 1 diabetes mellitus
  • diabetes duration of more than 5 years
  • no diabetic retinopathy on fundus examination or fundus photographs
  • no systemic hypertension (defined as systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)

• For control subjects :

  • sex and age matching with the diabetic patients
  • no diabetes, no familial or personal history of elevated blood sugar
  • Non-diabetic subjects, criteria defined by a fasting glucose <1.10 g / l and an HbA1c <6.5% (according to Lariboisière biochemistry laboratory HbA1c)
  • no systemic hypertension (defined as systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)
  • Subject with a normal ophthalmologic examination

• For both diabetic patients and control subjects :

  • Subject that has signed informed consent
  • Subject affiliated to a social security
  • Subject available for a period of 4 months

Exclusion Criteria:

• For both diabetic patients and control subjects :

  • presence of cataract or history of cataract surgery
  • intraocular pressure of more than 21 mmHg
  • treatment with vasoactive drugs
  • tobacco consumption of more than 20 cigarettes a day
  • Contraindications to trinitrin administration: hypersensitivity to trinitrin, treatment by sildenafil, heart disease, severe arterial hypotension, bradycardia, intracranial hypertension
  • Clinical Raynaud syndrome
  • Pregnant or breast-feeding subject
  • Subject whose age is <18 and> 60 years on the day of inclusion
  • Subject with cardiac disease, severe hypotension (BP <80/50 mmHg), a resting heart rate below 50 beats / minute
  • Subject intracranial hypertension
  • Subject with a current consumption of drugs or drugs that may impact vasomotion (antiglaucoma eye drops, vasodilators, antihypertensive drugs). Vasoactive drug use will be prohibited within 24 hours preceding the study.
  • Subject has not signed an informed consent
  • Subject not affiliated to a social security
  • Subject not available for a period of 4 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with type 1 diabetes; Diabetes duration >= 5 years, age >= 18 and <= 60 years old, patients with no visible diabetic retinopathy, and no arterial hypertension	Drug: Trinitrin; Trinitrin: 2 sublingual pulverisations of 0.3 mg/dose; Drug: Neosynephrine 10% collyrium; Neosynephrine 10% collyrium: 2 drops; Drug: Iontophoresis with acetylcholine delivery; Iontophoresis with acetylcholine delivery; Device: Dynamic Vessel Analyzer; Dynamic Vessel Analyzer
Healthy subjects; Sex and age-matched control healthy subjects	Drug: Trinitrin; Trinitrin: 2 sublingual pulverisations of 0.3 mg/dose; Drug: Neosynephrine 10% collyrium; Neosynephrine 10% collyrium: 2 drops; Drug: Iontophoresis with acetylcholine delivery; Iontophoresis with acetylcholine delivery; Device: Dynamic Vessel Analyzer; Dynamic Vessel Analyzer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of the presence of a retinal endothelial dysfunction in patients with type 1 diabetes mellitus with Dynamic vessel analyser(assessment study visit)	up to 4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Presence of a peripheral endothelial dysfunction	up to 4 months
Correlation between retinal and peripheral endothelial dysfunction (assessment study visit)	up to 4 months
Serum concentration of: CRP, ICAM-1, VCAM-1, VEGF, angiopoietin 2 and endostatin.	up to 4 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Amélie LECLEIRE-COLLET, MD, Assistance Publique - Hôpitaux de Paris; Principal Investigator: Pascale MASSIN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (Estimate): April 1, 2010

Study Record Updates

• Last Update Posted (Estimate): July 3, 2012
• Last Update Submitted That Met QC Criteria: July 2, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Endothelial dysfunction; Pathogenesis; Diabetic retinopathy; Type 1 diabetes mellitus; Dynamic Vessel Analyser
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Cholinergic Agonists; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Nitroglycerin; Phenylephrine; Acetylcholine
• Other Study ID Numbers: P080608; 2009-A0109552 (Other Identifier: Eudra CT)