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

Primary Purpose

Diabetic Retinopathy, Oxidative Stress, Diabetes

Status

Completed

Phase

Phase 2

Locations

Mexico

Study Type

Interventional

Intervention

Combined antioxidant therapy

Placebo

About this trial

This is an interventional treatment trial for Diabetic Retinopathy focused on measuring Vitreous humor, Vitrectomy, Aqueous humor, Antioxidant therapy, Oxidative markers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Institute of Experimental and Clinical Therapeutics,

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Combined Antioxidant Therapy group

Placebo group

Arm Description

This arm will be administered with the combined antioxidant therapy, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.

This arm will be administered with placebo, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT04071977

First Posted

August 26, 2019

Last Updated

March 21, 2022

Sponsor

University of Guadalajara

Collaborators

Hospital Civil de Guadalajara

1. Study Identification

Unique Protocol Identification Number

NCT04071977

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

March 25, 2020 (Actual)

Primary Completion Date

October 31, 2021 (Actual)

Study Completion Date

December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Guadalajara

Collaborators

Hospital Civil de Guadalajara

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Retinopathy, Oxidative Stress, Diabetes

Keywords

Vitreous humor, Vitrectomy, Aqueous humor, Antioxidant therapy, Oxidative markers

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Clinical trial phase IIa

Masking

ParticipantInvestigator

Masking Description

Drug

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combined Antioxidant Therapy group

Arm Type

Active Comparator

Arm Description

This arm will be administered with the combined antioxidant therapy, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

This arm will be administered with placebo, and will consist of 28 patients with proliferative diabetic retinopathy (PDR) who will undergo vitrectomy.

Intervention Type

Drug

Intervention Name(s)

Combined antioxidant therapy

Other Intervention Name(s)

Drusen Laz

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Magnesia

Intervention Description

It consists in a capsule with 100 mg of magnesium oxide

Primary Outcome Measure Information:

Title

Compare levels of markers of oxidative stress in aqueous humor and vitreous humor

Description

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

Time Frame

1 measure will be made after 2 months of intervention

Title

Changes in concentration of plasma 8-isoprostanes after intervention.

Description

Time Frame

2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention

Title

Changes in concentration of total antioxidant capacity (TAC) after intervention from baseline.

Description

Time Frame

2 measures will be made, 1 at baseline, and one after completion of 2 months of intervention

Secondary Outcome Measure Information:

Title

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.

Description

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

Time Frame

1 measure of glycated hemoglobin will be taken at baseline

Title

Description

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

Time Frame

1 measure of glycated hemoglobin will be taken at baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Institute of Experimental and Clinical Therapeutics,

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44340

Country

Mexico

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23875878

Citation

Rodriguez-Carrizalez AD, Castellanos-Gonzalez JA, Martinez-Romero EC, Miller-Arrevillaga G, Villa-Hernandez D, Hernandez-Godinez PP, Ortiz GG, Pacheco-Moises FP, Cardona-Munoz EG, Miranda-Diaz 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.

Results Reference

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PubMed Identifier

26207797

Citation

Rodriguez-Carrizalez AD, Castellanos-Gonzalez JA, Martinez-Romero EC, Miller-Arrevillaga G, Roman-Pintos LM, Pacheco-Moises FP, Miranda-Diaz 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.

Results Reference

background

PubMed Identifier

26321469

Citation

Rodriguez-Carrizalez AD, Castellanos-Gonzalez JA, Martinez-Romero EC, Miller-Arrevillaga G, Pacheco-Moises FP, Roman-Pintos LM, Miranda-Diaz 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.

Results Reference

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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

Results Reference

background

PubMed Identifier

31511825

Citation

Cecilia OM, Jose Alberto CG, Jose NP, Ernesto German CM, Ana Karen LC, Luis Miguel RP, Ricardo Raul 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.

Results Reference

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PubMed Identifier

32256949

Citation

Robles-Rivera RR, Castellanos-Gonzalez JA, Olvera-Montano C, Flores-Martin RA, Lopez-Contreras AK, Arevalo-Simental DE, Cardona-Munoz EG, Roman-Pintos LM, Rodriguez-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.

Results Reference

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PubMed Identifier

32962301

Citation

Lopez-Contreras AK, Martinez-Ruiz MG, Olvera-Montano C, Robles-Rivera RR, Arevalo-Simental DE, Castellanos-Gonzalez JA, Hernandez-Chavez A, Huerta-Olvera SG, Cardona-Munoz EG, Rodriguez-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):891. doi: 10.3390/antiox9090891.

Results Reference

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

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