Efficacy of Ubiquinone and Combined Antioxidant Therapy in Non-proliferative Diabetic Retinopathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of ubiquinone and combined antioxidant therapy on progression, clinical regression, oxidative stress markers and mitochondrial dysfunction in non-proliferative diabetic retinopathy.

Detailed Description
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The investigators are interested in demonstrating the efficacy of Ubiquinone and combined antioxidant therapy in the pharmacological management of diabetic retinopathy since early stages.

Official Title
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Efficacy of Ubiquinone and Combined Antioxidant Therapy on Progression, Oxidative Stress Markers and Mitochondrial Dysfunction in Non-proliferative Diabetic Retinopathy: A Phase 2a Randomized Double-blind Placebo-controlled Study

Conditions
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Non-proliferative Diabetic Retinopathy, Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Ubiquinone
* Drug: Combined antioxidant therapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes mellitus Patients with non proliferative diabetic retinopathy Glycated hemoglobin < 12.0% Signing of informed consent Exclusion Criteria: Patients with clinically significant macular edema Patients with diabetic retinopathy advanced lesions that have required or require specific treatment (laser, vitrectomy) Pretreatment with argon laser or excimer laser Ophthalmology surgery Any other associated ocular pathology (glaucoma, cataracts, changing cornea dystrophy, macular degeneration) Pregnancy, lactation, inadequate use of contraception Antioxidant drug and/or supplements six months previous to enrollment Renal and/or hepatic failure Age under 30 or over 75 years Severe cardiovascular disease (myocardial infarction, stroke, severe peripheral vasculopathy) Blood dyscrasias Have or have had cancer or other serious illness Neurodegenerative process Allergy to vitamins

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ubiquinone<br>400mg daily of oral ubiquinone for 24 weeks | Drug: Ubiquinone<br>* 400mg daily of oral ubiquinone for 24 weeks<br>* Other names: coenzyme Q10;|
| Experimental: Combined antioxidant therapy<br>(1mg copper + 20mg zinc + 180mg vitamin C + 30mg vitamin E + 1mg zeaxanthin + 4mg astaxanthin + 10mg lutein) daily of oral antioxidant combined therapy for 24 weeks | Drug: Combined antioxidant therapy<br>* (1 mg copper, 20 mg zinc, 180 mg vitamin C, 30 mg vitamin E, 1 mg zeaxanthin, 4 mg astaxanthin, 10 mg lutein) daily of oral, all of them in one Tablet for 24 weeks<br>* Other names: copper;|
| Placebo Comparator: Placebo<br>Placebo. 100mg daily oral intake for 24 weeks | Drug: Placebo<br>* 100 mg of oral placebo with identical appearance, form, size than ubiquinone and antioxidant combined therapy for 24 weeks<br>* Other names: Inactive drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative Stress markers | In this study the oxidative stress markers are composed of lipid peroxidation, nitric oxide, erythrocyte glutathion peroxidase activity, erythrocyte catalase activity, total antioxidant capacity and erythrocyte membrane fluidity. Lipid peroxidation (baseline and final values) given as malondialdehyde (MDA) and 4-hydroxyalkenals (4HDA) expressed in μmol/L Nitric oxide (NO) Levels of the NO catabolites nitrites/nitrates expressed in pmol/mL (baseline and final values) Erythrocyte glutathion peroxidase activity measured in U/min/mg protein (baseline and final values) Erythrocyte catalase activity expressed in U/mg protein (baseline and final values) Total antioxidant capacity measured in milliequivalent/mL (baseline and final values) Erythrocyte membrane fluidity, calculated using the fluorescence ratio of the excimer (Ie) to monomer (Im). The Ie/Im ratio. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitochondrial dysfunction markers | In this study the mitochondrial dysfunction markers are composed of hydrolysis of adenosine triphosphate and membrane fluidity in submitochondrial particles of platelets. Hydrolysis of adenosine triphosphate: The hydrolytic activity of mitochondrial F0/F1-ATPase (F0/F1-adenosine triphosphatase) was measured as the liberation of inorganic phosphate from platelet mitochondria. Expressed in nmol of phosphate. Baseline and final values. Membrane fluidity in submitochondrial particles of platelets. Calculated usig the fluorescence ratio of the excimer (Ie) to monomer (Im). The Ie/Im ratio. (Baseline and final values) | 24 weeks | 
| Progression and regression of non-proliferative diabetic retinopathy | Evaluated with International clinical diabetic retinopathy disease severity scale, fluorescein angiography and color fundus photographs. Baseline and final stage. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxidative stress, Mitochondrial dysfunction, Ubiquinone, Antioxidant combined therapy, Diabetic retinopathy