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Combined Antioxidant Therapy on Oxidative Stress in Aqueous and Vitreous Humor of Diabetic Retinopathy Patients

Phase 2
Completed
Conditions
Diabetic Retinopathy
Oxidative Stress
Diabetes
Interventions
Other: Placebo
Drug: Combined antioxidant therapy
Registration Number
NCT04071977
Lead Sponsor
University of Guadalajara
Brief Summary

The present study aims to support previous research on the effects of antioxidant therapy on the outcome of diabetic retinopathy and local oxidative stress values. The researchers intend to evaluate 56 patients with proliferative diabetic retinopathy undergoing the vitrectomy procedure, who will be assigned to a placebo group or combination antioxidant therapy. Each group will receive the intervention for 2 months. This intervention consists of taking one tablet (placebo or antioxidant therapy) orally, once a day.

At the beginning of the study, only blood samples will be collected to evaluate the state of oxidative and metabolic stress at a systemic level. After 2 months of intervention, blood samples will be taken again on the day of the intervention, adding the samples of aqueous and vitreous humor obtained during the vitrectomy. The results obtained between both groups and the different analysis matrices will be compared.

Detailed Description

Diabetic retinopathy is a diabetes microvascular complication due to an insufficient oxygen supply to its endothelial cells in states of constant hyperglycemia. This entity is classified in two main categories: non-proliferative diabetic retinopathy and proliferative diabetic retinopathy, the latter is characterized for the presence of neovascularization as oppose to the first one.

Oxidative stress has been considered as one of the main factors in the development of diabetic retinopathy. It is a result from an imbalance between oxidants production and cellular antioxidant defenses, which provokes DNA damage.

The treatment of diabetic retinopathy simply includes glycemic, lipemic and blood pressure control. Only when the view is compromised is when a vitrectomy is performed, which usually occurs in the more advanced stages such as the proliferative stage. Antioxidant therapy has been used as a coadjuvant for these interventions, complementing the action and efficacy of the treatment established for diabetic retinopathy in the early stages. However, in order to obtain vitreous and aqueous humor, the vitrectomy procedure is required, which is only carried out in the proliferative stage.

Diabetic retinopathy is a specific and chronic complication of diabetes mellitus and is known to have a prevalence of 43.6% internationally and 31.5% in the Mexican population. It represents the main cause of visual blindness and weakness in the economically active population, which also affects the quality of life and the productivity of the people who suffer it.

The researchers intend to evaluate whether antioxidant therapy influences the levels of oxidative stress markers at the ocular level.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Patients with type 2 with proliferative diabetic retinopathy
  • Blood pressure under 160/100 mmHg
  • HbA1c equal or lower than 9%
  • LDL under 190mg/dl, triglycerides under 500mg/dl)
  • Signed informed consent
  • Patients scheduled for vitrectomy surgery, under the following indications:
  • Severe vitreous hemorrhage lasting 1-3 months or longer, which does not go away spontaneously
  • Rhegmatogenous or tensile retina detachment
  • Epiretinal membrane that involves macula and that includes vitreomacular traction
Exclusion Criteria
  • Vitreous hemorrhage for any cause other than Proliferative Diabetic Retinopathy complication
  • Patients with vitrectomy surgery in the last 6 months
  • Patients with laser surgery in the last 6 months
  • Intravitreal application of antiangiogenic agents in the last 2 months
  • Patients with other ocular pathologies such as age-related macular degeneration, glaucoma, endophthalmitis, conjunctivitis of any etiology, severe lacrimal film dysfunction syndrome, etc.
  • Patients with concomitant systemic diseases such as: rheumatoid arthritis, sjogren's syndrome, upper respiratory tract infections, gastrointestinal infections, sepsis, any infectious process
  • Patients with severe cardiovascular disease (myocardial infarction, stroke, severe peripheral vascular disease)
  • Oral antioxidant intake that exceeds the daily recommendations in the last 6 months.
  • Consumption of pharmacological agents such as: immunomodulators, biological, anti-inflammatory, in the last 3 months
  • Smokers
  • Patients with neurodegenerative or carcinogen processes
  • Patients who are currently participating in other clinical trials

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo groupPlaceboThis arm will be administered with placebo, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.
Combined Antioxidant Therapy groupCombined antioxidant therapyThis arm will be administered with the combined antioxidant therapy, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.
Primary Outcome Measures
NameTimeMethod
Compare levels of markers of oxidative stress in aqueous humor and vitreous humor1 measure will be made after 2 months of intervention

The investigators will measure oxidative stress markers in aqueous and vitreous humor taken during vitrectomy procedure and compare such results between both intervention groups.

Changes in concentration of plasma 8-isoprostanes after intervention.2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention

The investigators will consider changes presented in plasma concentrations of 8-isoprostanes from baseline to the end of the intervention. The investigators expect to find a decrease in 8-isoprostanes concentrations in the supplemented group.

Changes in concentration of total antioxidant capacity (TAC) after intervention from baseline.2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention

The investigators will consider changes presented in plasma concentrations of total antioxidant capacity (TAC) from baseline to the end of the intervention. The investigators expect to find TAC augmentation in the supplemented group.

Secondary Outcome Measures
NameTimeMethod
Correlate the levels of 8-isoprostanes in systemic samples, aqueous humor and vitreous humor with the glycosylated hemoglobin value of patients with proliferative diabetic retinopathy.1 measure of glycated hemoglobin will be taken at baseline

The investigators will consider levels of 8-isoprostanes in serum, aqueous humor and vitreous humor after intervention and baseline glycated hemoglobin

Correlate the levels of total antioxidant capacity (TAC) in systemic samples, aqueous humor and vitreous humor with the glycosylated hemoglobin value of patients with proliferative diabetic retinopathy.1 measure of glycated hemoglobin will be taken at baseline

The investigators will consider levels of total antioxidant capacity in serum, aqueous humor and vitreous humor after intervention and baseline glycated hemoglobin

Trial Locations

Locations (1)

Institute of Experimental and Clinical Therapeutics,

🇲🇽

Guadalajara, Jalisco, Mexico

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