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

NCT03702374 | Completed Phase 3 DMC

• 1 other identifier: RD-20170102
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Retinopathy

Keywords

diabetic retinopathy; oxidative stress; mitochondrial dysfunction; oxidative markers; diabetes; antioxidant therapy

Outcome Measures

Primary Outcomes (3)

• Changes in concentration of serum malondialdehyde after 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

  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.

  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 Outcomes (1)

• Diabetic retinopathy severity progress at the end of intervention from baseline

  2 measures will be made, 1 at baseline and a second one after 12 months of intervention.

Study Arms (2)

Combined Antioxidant Therapy group

EXPERIMENTAL

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

Placebo group

PLACEBO COMPARATOR

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

Interventions

Combined antioxidant therapy DRUG

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

Also known as: Drusen Laz

Combined Antioxidant Therapy group

Placebo OTHER

It consists in a capsule with 100mg of magnesium oxide.

Also known as: Magnesia

Placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Guadalajara: lead
• Instituto Mexicano del Seguro Social: 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

• 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

• 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

• 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

MeSH Terms

Conditions

Diabetic Retinopathy; Mitochondrial Diseases; Diabetes Mellitus

Interventions

Magnesium Oxide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Adolfo D. Rodriguez-Carrizalez, PhD

  Clinical Investigator at University of Guadalajara

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 11, 2018
• Study Start: September 26, 2018
• Primary Completion: November 30, 2020
• Study Completion: December 31, 2020
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)