Restoration of Retinal Vascular Responses in Type 1 Diabetic Patients

NCT ID: NCT02099981

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2017-12-31

Brief 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.

Conditions

Diabetic Retinopathy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Control Group

Control subjects will receive AG.

Group Type: EXPERIMENTAL

Aminoguanidine

Intervention Type: DRUG

Type 1 diabetes

Type 1 diabetic subjects will receive AG.

Group Type: EXPERIMENTAL

Aminoguanidine

Intervention Type: DRUG

Interventions

Aminoguanidine

Intervention Type: DRUG

Other Intervention Names

AG

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes between 18 and 65 years of age
• Diabetes duration between 5 to 20 years.
• Normal report or minor findings on a dilated eye exam
• Healthy subjects on no medications

Exclusion Criteria

Current diagnosis or history of:

• hypertension
• dyslipidemia
• epilepsy
• glaucoma or other ocular disease
• renal insufficiency/failure (creatinine >1.5 mg/dL)
• pregnancy or breastfeeding.
• smoker

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Seaquist, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota Medical Center Fairview

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

Protocol 22503

Identifier Type: -

Identifier Source: org_study_id