Clinical trial NCT00411333: Vascular Remodeling and the Effects of Angiogenic Inhibition in Diabetic Retinopathy
Official title: Vascular Remodeling and the Effects of Angiogenic Inhibition in Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Diabetic Retinopathy
Keywords: diabetic retinopathy
fluorescein angiography
steroid
anti-angiogenesis
Lead sponsor: National Eye Institute (NEI)
Sponsor class: NIH
First posted: 2006-12-14
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The retinal vasculature changes dramatically in patients with diabetic retinopathy especially between non-proliferative and proliferative disease. The retinal vasculature can be imaged and quantified using special dyes. This study will test whether the pattern of the retinal vasculature changes in patients with different levels of diabetic retinopathy can be quantified using computerized image analysis. In addition, the study will evaluate whether new drugs to treat diabetic retinopathy will be able to reverse these vascular changes.

Detailed description: In this study, we are studying whether vascular density decreases during diabetic retinopathy prior to the pathological neovascularization seen in proliferative disease that results in blindness in more than 50 percent of patients, and whether the adverse, early vascular remodeling and neovascularization can be reversed by anti-angiogenic therapeutics. We have shown that vascular density decreases during early stages of diabetic retinopathy, prior to the pathological neovascularization that defines proliferative retinopathy, and that this change may be reversible with new anti-angiogenic therapeutics. To test this hypothesis we will determine (1) how blood vessels remodel and whether vascular density truly decreases during diabetic retinopathy and (2) how the anti-angiogenic steroid triamcinolone acetonide affects vascular density and pattern during human diabetic retinopathy and in our experimental model, the avian CAM model.

Twenty patients (n = 20) for each of the 4 NPDR stages will be enrolled. In addition, a control group of 20 normal subjects will be recruited from the same clinical practice that do not have diabetes and no evidence of any vascular disease, for a total of 100 patients in the clinical trial.

Eligibility criteria: Inclusion Criteria:

- Presence of mild, moderate, severe, or very severe non-proliferative diabetic retinopathy (defined as ETDRS level \>10) in at least one eye (based on ETDRS criteria)

Exclusion Criteria:

* Any condition that might impair the patient's ability to give informed consent
* Any condition or media opacity that might impair the patient's ability to perform vision tests, color fundus photographs or fluorescein angiography
* Severe allergy or other contraindication to sodium fluorescein dye
* Participating in any other ophthalmic clinical trial

Primary outcomes:
measure: Change in retinal vascular density from baseline on fluorescein angiography
Secondary outcomes:
measure: Safety
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cole Eye Institute
state: Ohio
Study officials:
affiliation: Cole Eye Institute
name: Peter K Kaiser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parsons-Wingerter P, Radhakrishnan K, Vickerman MB, Kaiser PK. Oscillation of angiogenesis with vascular dropout in diabetic retinopathy by VESsel GENeration analysis (VESGEN). Invest Ophthalmol Vis Sci. 2010 Jan;51(1):498-507. doi: 10.1167/iovs.09-3968. Epub 2009 Sep 24.
citation: Vickerman MB, Keith PA, McKay TL, Gedeon DJ, Watanabe M, Montano M, Karunamuni G, Kaiser PK, Sears JE, Ebrahem Q, Ribita D, Hylton AG, Parsons-Wingerter P. VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks. Anat Rec (Hoboken). 2009 Mar;292(3):320-32. doi: 10.1002/ar.20862.