Restoration of Retinal Vascular Responses in Type 1 Diabetic Patients
Condition: Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy
Study type: Interventional
Phase: Phase 1

Summary: 
      Diabetic retinopathy is the leading cause of blindness in the developed world. The causes of
      the disease are poorly understood. One of the earliest changes that occur in the retinas of
      diabetic patients, well before overt retinopathy is observed, is a reduction in light-evoked
      increases in blood flow in retinal vessels. The loss of this vascular response may lead to
      retinal hypoxia and it has been suggested that hypoxia could be a principal cause of diabetic
      retinopathy.

      The long-term goals of this project are to determine whether decreased blood flow in diabetic
      patients and the resulting retinal hypoxia contributes to the development of diabetic
      retinopathy and whether restoration of normal blood flow in diabetic patients slows or
      prevents the development of retinopathy.
    

Detailed description: 
      The immediate goal of the proposed project is to determine whether administration of
      aminoguanidine (AG) restores light--evoked vasodilations in the retinas of patients without
      advanced retinopathy. We will also determine whether AG improves contrast sensitivity in
      diabetic patients. The proposed experiments are as a first step in developing new therapies
      to prevent diabetic retinopathy.

      Study participants will be asked to come to the University of Minnesota on three (3)
      occasions (the visits will last for up to 2, 5 and 3 hours respectively).

      Visit 1. During the screening visit (first and shortest visit), consent will be obtained and
      baseline labs collected (Hemoglobin A1c and Creatinine). Demographic information (date of
      birth, gender, race), subjects characteristics (weight, height, blood pressure and pulse) and
      relevant medical history will be recorded.

      Visit 2. Vessel dilation testing: Control and diabetic subjects will present to the
      Ophthalmology Research Unit at the University of Minnesota. Prior to the imaging examination,
      each subject will receive dilating eye drops (1% Tropicamide) to prevent accommodation of the
      pupil and brief eye exam will be performed. Measurement of resting vessel diameter and
      light--evoked vessel dilation will be made using the Imedos Systems "Dynamic Vessel
      Analyzer". Subjects will be instructed to look at a fixation spot and a 350 s sequence of
      fundus images will be acquired during baseline and stimulation period. After completion of
      the initial vasodilation measurements, both control and diabetic subjects will be given 150
      mg AG orally and measurement of resting vessel diameter and light--evoked vasodilation will
      be repeated 90 minutes later.

      Visit 3. Contrast sensitivity testing: Contrast sensitivity will be assessed in un-dilated
      control and diabetic subjects. Contrast sensitivity will be determined both before and after
      AG administration using a CSV-100 test chart (VectorVision) and will be measured at 3, 6, 12,
      and 18 cycles per degree.
    

Intervention name(s): Aminoguanidine
Intervention type(s): Drug
Other intervention name(s): AG
Intervention MeSH terms: Pimagedine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Diabetes; Diabetic; Retinopathy; Ophthalmology; Eye; Eyes