Effects of Pulsatile IV Insulin Delivery on Diabetic Retinopathy in Patients With Types 1 and 2 Diabetes Mellitus
|Diabetes Mellitus, With Complications||Procedure: Pulsatile IV Insulin Procedure: Effects of Pulsatile IV Insulin on Diabetic Retinopathy||Phase 2 Phase 3|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Pulsatile IV Insulin Delivery on Diabetic Retinopathy|
- Serial fundus photography [ Time Frame: Stabilization of retinal blood vessel degeneration ]
|Study Start Date:||November 2005|
|Study Completion Date:||August 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
Active Comparator: 2
Patients with diagnosed Diabetic Retinopathy are enrolled as treated with pulsatile intravenous insulin or as a control patient with weekly treatment sessions. Baseline and quarterly fundus photography is performed to measure and monitor progress.
Procedure: Pulsatile IV Insulin
Intravenous Insulin is provided in a pulsed manner based upon weekly physician orders the amount of insulin provided is dependent on patients level of insulin resistance.Procedure: Effects of Pulsatile IV Insulin on Diabetic Retinopathy
Control Patients are not given pulsatile intravenous insulin therapy during the study.Procedure: Effects of Pulsatile IV Insulin on Diabetic Retinopathy
Intravenous Insulin is provided in a pulsed manner based upon weekly physician orders the amount of insulin provided is dependent on patients level of insulin resistance.
Other Name: Humilin, Humolog, Novolog, Epidra
No Intervention: 1
Patients diagnosed with Diabetic Retinopathy are enrolled as control patients that do not receive the pulsatile intravenous insulin therapy. Control patients come into the center receive baseline fundus photography and quarterly fundus photography to measure progress and outcomes of diabetic retinopathy and are compared to the patients who receive pulsatile intravenous insulin therapy.
Diabetic retinopathy is one of the leading causes of blindness in the world. Signs of retinopathy are detected in almost 100% of type 1 diabetic patients who have had their disease for at least 20 years and almost 100% of type 2 diabetic patients with the similar duration of disease (1). Histopathologic findings range from microaneurysms and cotton wool spots to more ominous neovascularization. The latter process, known as proliferative diabetic retinopathy, can progress to total blindness if untreated. The biochemical mechanisms responsible for PDR have been extensively studied, and appear to be multifactorial. Associated findings include abnormalities of vasoactive peptides such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), and insulin-like growth factor (ILF-1), lipids, oxidative pathways, enzymatic pathways, such as protein kinase, and carbohydrate metabolism (1-4). Whether these (and other) factors are interrelated or have a common underlying defect is unknown. The common endpoint, however, is vascular leakage with neovascularization. Current therapeutic regimens based on these biochemical abnormalities have to date been unsuccessful in stemming the progression of proliferative diabetic retinopathy. Current treatment strategies emphasize glycemic and blood pressure control, with laser photocoagulation and vitrectomy for advanced cases (5).
Early retinal disease in diabetic patients may take the form of diabetic macular edema (DME). This is observed in 20% to 25% of both type 1 and type 2 diabetic patients. The pathophysiology of DME involves the leakage of plasma from small vessels in the macula. Resorption of this fluid followed by hard exudate formation can lead to severe impairment of central vision (6).
Anecdotal evidence from ophthalmologic institutions (Houston Eye Institute, Shands at University of Florida, Bascom Palmer Eye Institute) suggests that this treatment arrests the progression of retinal disease in patients with proliferative diabetic retinopathy. The mechanism of this effect is unknown, but may be related to reversal of retinal ischemia or downregulation of vasoactive peptides by restoration of hepatic metabolism.
This study is designed as a prospective, controlled, single blinded evaluation of pulsatile insulin in the role of diabetic retinopathy. The patients entered into the study will be from two distinct sources. First, in conjunction with a national eye imaging company, patients with known type 1 or type 2 diabetes will be evaluated for retinal disease. This evaluation will consist of mydriatic fundus photography in diabetic patients not having had recent ophthalmologic evaluation (period greater than 12 months). The fundus photographs will be read by an observer under the auspices of the Wilmer Ophthalmologic Institute at Johns Hopkins Hospital. Classifications of patients will be evaluated in this study include:
I Patients with non high risk proliferative diabetic retinopathy II Patients with severe non proliferative diabetic retinopathy
Patients who are diagnosed as one of these classifications will be offered entrance into the study. Study patients will be matched for age, sex, and disease severity into a treatment and control group. All study patients will be evaluated in conjunction with an ophthalmologist. This evaluation will include clinical examination and fundus photography. Treatment group patients will undergo weekly pulsatile insulin delivery sessions as per protocol above. Control group patients will have weekly clinic visits to maximize glycemic and hypertensive control. All patients will repeat their fundus photography at three month intervals, with ophthalmologic evaluation as above every six months, or more often if requested by the ophthalmologist.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00287651
|United States, Florida|
|Florida Atlantic University Center for Complex Systems and Brain Sciences|
|Boca Raton, Florida, United States, 33431|
|Principal Investigator:||Betty Tuller, Ph.D||Florida Atlantic University|