Combined Antioxidant Therapy on Oxidative Stress, Mitochondrial Dysfunction Markers in Diabetic Retinopathy
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|ClinicalTrials.gov Identifier: NCT03702374|
Recruitment Status : Recruiting
First Posted : October 11, 2018
Last Update Posted : October 29, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Diabetic Retinopathy||Drug: Combined antioxidant therapy Other: Placebo||Phase 3|
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 (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Effect of Prolonged Combined Antioxidant Therapy Intake on Oxidative Stress and Mitochondrial Dysfunction Markers in Patients With Diabetic Retinopathy|
|Actual Study Start Date :||September 26, 2018|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||November 1, 2020|
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 Name: 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.
It consists in a capsule with 100mg of magnesium oxide.
Other Name: Magnesia
- 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.
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03702374
|Contact: Adolfo D. Rodríguez-Carrizalez, PhD||10585200 ext email@example.com|
|Contact: Cecilia Olvera-Montaño, MD||10585200 ext firstname.lastname@example.org|
|Institute of Experimental and Clinical Therapeutics,||Recruiting|
|Guadalajara, Jalisco, Mexico, 44340|
|Contact: Adolfo D. Rodriguez-Carrizalez, PhD +52 33 10585200 ext 33658 email@example.com|
|Contact: Cecilia Olvera-Montaño, MD +52 33 10 58 52 00 ext 33658 firstname.lastname@example.org|
|Sub-Investigator: Cecilia Olvera-Montaño, MD|
|Sub-Investigator: José A. Castellanos-González, MSc|
|Sub-Investigator: Alejandra G Miranda-Díaz, PhD|
|Study Director:||Adolfo D. Rodriguez-Carrizalez, PhD||Clinical Investigator at University of Guadalajara|