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

NCT04071977 | Completed Phase 2

• 1 other identifier: RD-20180831
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Retinopathy; Oxidative Stress; Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• 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

• 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

Study Arms (2)

Combined Antioxidant Therapy group

ACTIVE COMPARATOR

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.

Drug: Combined antioxidant therapy

Placebo group

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Combined antioxidant therapy DRUG

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

Also known as: Drusen Laz

Combined Antioxidant Therapy group

Placebo OTHER

It consists in a capsule with 100 mg of magnesium oxide

Also known as: Magnesia

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Guadalajara: lead
• Hospital Civil de Guadalajara: collaborator

Study Sites (1)

Institute of Experimental and Clinical Therapeutics,

Guadalajara, Jalisco, 44340, Mexico

Location

Related Publications (7)

• 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.

  PMID: 23875878 BACKGROUND

• 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.

  PMID: 26207797 BACKGROUND

• 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.

  PMID: 26321469 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 31511825 BACKGROUND

• 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.

  PMID: 32256949 BACKGROUND

• 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.

  PMID: 32962301 BACKGROUND

MeSH Terms

Conditions

Diabetic Retinopathy; Diabetes Mellitus

Interventions

Magnesium Oxide

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Drug
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Clinical trial phase IIa

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 28, 2019
• Study Start: March 25, 2020
• Primary Completion: October 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)