Combined Antioxidant Therapy on Oxidative Stress, Mitochondrial Dysfunction Markers in Diabetic Retinopathy

March 21, 2022 updated by: Adolfo Daniel Rodriguez-Carrizalez, University of Guadalajara

Effect of Prolonged Combined Antioxidant Therapy Intake on Oxidative Stress and Mitochondrial Dysfunction Markers in Patients With Diabetic Retinopathy

The present study aims to support previous research on antioxidant therapy effects in diabetic retinopathy outcome. The investigators intend to assess 180 patients with diabetic retinopathy in different stages (moderate, severe and proliferative), whom either will be assigned to placebo group or combined antioxidant therapy. Each group will receive the intervention for 12 months. Such intervention consists in taking one tablet (placebo or antioxidant therapy) orally, a day.

At baseline, blood and urine samples will be collected in order to assess metabolic and oxidative stress status, mitochondrial function or dysfunction, liver and kidney function. In addition, fluorescein angiography will be done for the categorization of diabetic retinopathy. After six months and at the end of the intervention, blood and urine measurements as well as angiographies will be done for comparing the outcomes between both groups and correlate oxidative stress status, mitochondrial dysfunction with grade of retinopathy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 results from an imbalance between oxidants production and cellular antioxidant defenses, which provokes DNA damage in the mitochondrion altering its capacity to produce ATP (Adenosine Triphosphate) resulting in what is known as mitochondrial dysfunction.

Diabetic retinopathy management merely comprises glycemic, lipemic and blood pressure control. Secondary intervention includes anti-platelet agents, protein-kinase C inhibitors, aldolase reductase inhibitors, laser and vitrectomy. Antioxidant therapy has been used as a co-adjuvant for these interventions, as antioxidant substances that complement action and efficacy of the established treatment for diabetic retinopathy.

Diabetic retinopathy is the principal cause of blindness in persons between 20 and 70 years of age. Its prevalence is, approximately, 25% 5 years after diagnosis.

Which is why the investigators intend to prove if the antioxidant therapy is able to change retinopathy outcomes in oxidative stress, mitochondrial dysfunction and/or grade of retinopathy.

Study Type

Interventional

Enrollment (Actual)

132

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Institute of Experimental and Clinical Therapeutics,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with type 2 diabetes with moderate or severe non-proliferative diabetic retinopathy without clinically significant macular edema.
  • Patients with type 2 diabetes with proliferative diabetic retinopathy without clinically significant macular edema.
  • In current treatment that may include: metformin, glibenclamide, pravastatin, bezafibrate, losartan, nifedipine or captopril.
  • HbA1c equal or lower than 9%
  • LDL under 190mg/dl, triglycerides under 500mg/dl)
  • Blood pressure under 180/110 mmHg
  • Non-smoker or inactive for at least 6 months
  • Signed informed consent

Exclusion Criteria:

  • Antioxidant therapy intake over the last 6 months. Antioxidant dietary intake that surpasses the daily DIR (dietary intake recommendations)
  • Patients who require secondary intervention (laser surgery)
  • Patients with previous history of myocardial infarction, ictus or severe peripheral vasculopathy
  • Patients with pathologies that increase oxidative stress
  • Patients with neurodegenerative or carcinogen processes
  • Hepatic or renal failure
  • Pregnancy
  • Patients with hypersensitivity to therapy components
  • Other ocular pathologies, such as cataract, glaucoma, corneal dystrophy, macular degeneration among others
  • Patients who are currently participating in other clinical trials

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Combined Antioxidant Therapy group
This arm will be administered with the combined antioxidant therapy, and will consist of 30 patients with moderate non-proliferative diabetic retinopathy (NPDR), 30 subjects with severe NPDR and 30 patients with Proliferative diabetic retinopathy.
Drug: Combined antioxidant therapy
It consists in a tablet with lutein (10 mg), astaxanthin (4 mg), Zeaxanthin (1mg), vitamin C (L-ascorbic acid 180mg), vitamin E (DL-alpha tocopherol 30mg), zinc (zinc oxide 20mg), copper (copper sulfate 1mg), taken once a day for 12 months
Other Names:
  • Drusen Laz
PLACEBO_COMPARATOR: Placebo group
This arm will be administered with placebo, and will consist of 30 patients with moderate non-proliferative diabetic retinopathy (NPDR), 30 subjects with severe NPDR and 30 patients with Proliferative diabetic retinopathy.
Other: Placebo
It consists in a capsule with 100mg of magnesium oxide.
Other Names:
  • Magnesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in concentration of serum malondialdehyde after intervention.
Time Frame: 3 measures will be made, 1 at baseline, another one after 6 months and a last one after completion of 12 months of intervention.
The investigators will consider changes presented in plasma concentrations of malondialdehyde from baseline to the end of the intervention. The investigators expect to find a decrease in malondialdehyde concentrations in the supplemented group.
3 measures will be made, 1 at baseline, another one after 6 months and a last one after completion of 12 months of intervention.
Changes in ATPase activity after intervention from baseline
Time Frame: 3 measures will be made, 1 at baseline, another one after 6 months and a last one after 12 months of intervention
The investigators will consider changes showed in ATPase activity after the intervention compared to baseline. The investigators expect to find a decrease in ATPase activity in the supplemented group.
3 measures will be made, 1 at baseline, another one after 6 months and a last one after 12 months of intervention
Changes in concentration of total antioxidant capacity (TAC) after intervention from baseline.
Time Frame: 3 measures will be made, 1 at baseline, another one after 6 months and a last one after 12 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.
3 measures will be made, 1 at baseline, another one after 6 months and a last one after 12 months of intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diabetic retinopathy severity progress at the end of intervention from baseline
Time Frame: 2 measures will be made, 1 at baseline and a second one after 12 months of intervention.

Change in grade of retinopathy according to the International Clinical Diabetic Retinopathy Disease Severity Scale.

No apparent retinopathy: No abnormalities. Mild non-proliferative diabetic retinopathy: presence of microaneurysms only. Moderate non-proliferaitve diabetic retinopathy: More than just microaneurysms but less than Severe Non-proliferative diabetic retinopathy.

Severe non-proliferative diabetic retinopathy: Presence of more than 20 intraretinal hemorrhages in each of 4 quadrants, venous beading in 2 or more quadrants, prominent intraretinal microvascular anormalities in one or more quadrants, no signs of proliferative retinopathy.

Proliferative diabetic retinopathy: presence of neovascularization, or vitreous/preretinal hemorrhage.

Note: Progression from a moderate non-proliferative diabetic retinopathy to a severe non-proliferative diabetic retinopathy, and from either of those two to proliferative retinopathy will be considered as a worse outcome.
2 measures will be made, 1 at baseline and a second one after 12 months of intervention.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Guadalajara

Collaborators

Instituto Mexicano del Seguro Social

Investigators

  • Study Director: Adolfo D. Rodriguez-Carrizalez, PhD, Clinical Investigator at University of Guadalajara

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 26, 2018

Primary Completion (ACTUAL)

November 30, 2020

Study Completion (ACTUAL)

December 31, 2020

Study Registration Dates

First Submitted

October 2, 2018

First Submitted That Met QC Criteria

October 9, 2018

First Posted (ACTUAL)

October 11, 2018

Study Record Updates

Last Update Posted (ACTUAL)

April 1, 2022

Last Update Submitted That Met QC Criteria

March 21, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RD-20170102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The results of this study will be published in an open access journal with impact factor according to Journal Citation Reports. Considering the global clinical status of participants before and after of pharmacological intervention.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetic Retinopathy

Clinical Trials on Combined antioxidant therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe