Endothelial Dysfunction and Diabetes (DENDI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01097551
First received: March 31, 2010
Last updated: July 2, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Type 1 Diabetes Mellitus
Drug: Trinitrin
Drug: Neosynephrine 10% collyrium
Drug: Iontophoresis with acetylcholine delivery
Device: Dynamic Vessel Analyzer

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Assessment of Endothelial Dysfunction in Retinal and Peripheral Retinal Vessels in Diabetes

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Evaluation of the presence of a retinal endothelial dysfunction in patients with type 1 diabetes mellitus with Dynamic vessel analyser(assessment study visit) [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Presence of a peripheral endothelial dysfunction [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
  • Correlation between retinal and peripheral endothelial dysfunction (assessment study visit) [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
  • Serum concentration of: CRP, ICAM-1, VCAM-1, VEGF, angiopoietin 2 and endostatin. [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: January 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
Other Name: Neosynephrine 10% collyrium
Drug: Iontophoresis with acetylcholine delivery
Iontophoresis with acetylcholine delivery
Other Name: Iontophoresis with acetylcholine delivery
Device: Dynamic Vessel Analyzer
Dynamic Vessel Analyzer
Other Name: 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
Other Name: Neosynephrine 10% collyrium
Drug: Iontophoresis with acetylcholine delivery
Iontophoresis with acetylcholine delivery
Other Name: Iontophoresis with acetylcholine delivery
Device: Dynamic Vessel Analyzer
Dynamic Vessel Analyzer
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01097551

Locations
France
Hôpital LARIBOISIERE Service d'Ophtalmologie
Paris, France, 75010
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01097551     History of Changes
Other Study ID Numbers: P080608, 2009-A0109552
Study First Received: March 31, 2010
Last Updated: July 2, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Type 1 diabetes mellitus
Diabetic retinopathy
Pathogenesis
Dynamic Vessel Analyser
Endothelial dysfunction

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Acetylcholine
Nitroglycerin
Oxymetazoline
Phenylephrine
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nasal Decongestants
Vasoconstrictor Agents
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists

ClinicalTrials.gov processed this record on July 24, 2014