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

Diabetes Clinical Trial

Official title:

Effect of Combined Antioxidant Therapy on the Levels of Oxidative Stress Markers in Aqueous and Vitreous Humor of Patients With Proliferative Diabetic Retinopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04071977
• Other study ID #: RD-20180831
• Status: Completed
• Phase: Phase 2
• Start date: March 25, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2022
• Source: University of Guadalajara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 31, 2021
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetic Retinopathy
• Oxidative Stress
• Retinal Diseases

Intervention

Drug:
• Combined antioxidant therapy
It consists of a tablet with lutein (10 mg), astaxanthin (4 mg), Zeaxanthin (1 mg), vitamin C (L-ascorbic acid 180 mg), vitamin E (DL-alpha tocopherol 30 mg), zinc (zinc oxide 20 mg), copper (copper sulfate 1 mg), taken once a day for 12 months

Other:
• Placebo
It consists in a capsule with 100 mg of magnesium oxide

Locations

Country	Name	City	State
Mexico	Institute of Experimental and Clinical Therapeutics,	Guadalajara	Jalisco

Sponsors (2)

Lead Sponsor	Collaborator
University of Guadalajara	Hospital Civil de Guadalajara

Country where clinical trial is conducted

Mexico, 

References & Publications (7)

Cecilia OM, José Alberto CG, José NP, Ernesto Germán CM, Ana Karen LC, Luis Miguel RP, Ricardo Raúl RR, Adolfo Daniel RC. Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology. J Diabetes Res. 2019 Aug 14;2019:8562408. doi: 10.1155/2019/8562408. eCollection 2019. Review. — View Citation

López-Contreras AK, Martínez-Ruiz MG, Olvera-Montaño C, Robles-Rivera RR, Arévalo-Simental DE, Castellanos-González JA, Hernández-Chávez A, Huerta-Olvera SG, Cardona-Muñoz EG, Rodríguez-Carrizalez AD. Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy. Antioxidants (Basel). 2020 Sep 20;9(9). pii: E891. doi: 10.3390/antiox9090891. Review. — View Citation

Robles-Rivera RR, Castellanos-González JA, Olvera-Montaño C, Flores-Martin RA, López-Contreras AK, Arevalo-Simental DE, Cardona-Muñoz EG, Roman-Pintos LM, Rodríguez-Carrizalez AD. Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation. Oxid Med Cell Longev. 2020 Mar 11;2020:3096470. doi: 10.1155/2020/3096470. eCollection 2020. Review. — View Citation

Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, Miller-Arrevillaga G, Pacheco-Moisés FP, Román-Pintos LM, Miranda-Díaz AG. The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study. Redox Rep. 2016 Jul;21(4):155-63. doi: 10.1179/1351000215Y.0000000040. Epub 2015 Aug 31. — View Citation

Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, Miller-Arrevillaga G, Román-Pintos LM, Pacheco-Moisés FP, Miranda-Díaz AG. The antioxidant effect of ubiquinone and combined therapy on mitochondrial function in blood cells in non-proliferative diabetic retinopathy: A randomized, double-blind, phase IIa, placebo-controlled study. Redox Rep. 2016 Jul;21(4):190-5. doi: 10.1179/1351000215Y.0000000032. Epub 2016 Feb 5. — View Citation

Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, Miller-Arrevillaga G, Villa-Hernández D, Hernández-Godínez PP, Ortiz GG, Pacheco-Moisés FP, Cardona-Muñoz EG, Miranda-Díaz AG. Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic retinopathy. J Diabetes. 2014 Mar;6(2):167-75. doi: 10.1111/1753-0407.12076. Epub 2013 Aug 21. — View Citation

Sonia Sifuentes-Franco, Adolfo Daniel Rodríguez-Carrizalez, Sandra Carrillo- Ibarra, José Alberto Castellanos-González, Esaú César Martínez-Romero, Guillermo Miller-Arrevillaga and Alejandra Guillermina Miranda-Díaz. The effect of Ubiquinone administration on oxidative DNA damage and repair in plasma levels in non-proliferative diabetic retinopathy.Diabetes Management 2017;7(2):186-191

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare levels of markers of oxidative stress in aqueous humor and vitreous humor	The investigators will measure oxidative stress markers in aqueous and vitreous humor taken during vitrectomy procedure and compare such results between both intervention groups.	1 measure will be made after 2 months of intervention
Primary	Changes in concentration of plasma 8-isoprostanes after 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.	2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention
Primary	Changes in concentration of total antioxidant capacity (TAC) after intervention from baseline.	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.	2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention
Secondary	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.	The investigators will consider levels of 8-isoprostanes in serum, aqueous humor and vitreous humor after intervention and baseline glycated hemoglobin	1 measure of glycated hemoglobin will be taken at baseline
Secondary	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.	The investigators will consider levels of total antioxidant capacity in serum, aqueous humor and vitreous humor after intervention and baseline glycated hemoglobin	1 measure of glycated hemoglobin will be taken at baseline