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

Sponsor

University of Guadalajara (Other)

Overall Status

Completed

CT.gov ID

NCT02062034

Collaborator

Instituto Mexicano del Seguro Social (Other)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-proliferative Diabetic Retinopathy Diabetes Mellitus Type 2	Drug: Ubiquinone Drug: Combined antioxidant therapy Drug: Placebo	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ubiquinone 400mg daily of oral ubiquinone for 24 weeks	Drug: Ubiquinone 400mg daily of oral ubiquinone for 24 weeks Other Names: coenzyme Q10
Experimental: Combined antioxidant therapy (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 (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 Other Names: lutein zeaxanthin astaxanthin vitamin C vitamin E zinc copper
Placebo Comparator: Placebo Placebo. 100mg daily oral intake for 24 weeks	Drug: Placebo 100 mg of oral placebo with identical appearance, form, size than ubiquinone and antioxidant combined therapy for 24 weeks Other Names: Inactive drug

Arm

Intervention/Treatment

Experimental: Ubiquinone

400mg daily of oral ubiquinone for 24 weeks

Drug: Ubiquinone

400mg daily of oral ubiquinone for 24 weeks

Other Names:

coenzyme Q10

Experimental: Combined antioxidant therapy

(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

(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

Other Names:

lutein

zeaxanthin

astaxanthin

vitamin C

vitamin E

zinc

copper

Placebo Comparator: Placebo

Placebo. 100mg daily oral intake for 24 weeks

Drug: Placebo

100 mg of oral placebo with identical appearance, form, size than ubiquinone and antioxidant combined therapy for 24 weeks

Other Names:

Inactive drug

Outcome Measures

Primary Outcome Measures

Oxidative Stress markers [24 weeks]
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.

Secondary Outcome Measures

Mitochondrial dysfunction markers [24 weeks]
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)
Progression and regression of non-proliferative diabetic retinopathy [24 weeks]
Evaluated with International clinical diabetic retinopathy disease severity scale, fluorescein angiography and color fundus photographs. Baseline and final stage.

Other Outcome Measures

Security profile [24 weeks]
In this study the security profile markers are composed of intraocular pressure, visual acuity, renal function, and liver profile. Intraocular pressure. expressed in mmHg (baseline and final values) Visual acuity measured in decimal scale (baseline and final values) Renal function: serum urea (mg/dL), serum creatinine (mg/dL). (Baseline and final values) Liver profile: total serum bilirubin (mg/dL), indirect bilirubin (mg/dL), direct bilirubin (mg/dL) (Baseline and final values).

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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