Effect of Topical Antioxidants in Dry Eye Disease and Diabetic Retinopathy

NCT05429229 | Unknown Phase 2 DMC

• 1 other identifier: OSRD-20200831-1
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of our study is to evaluate the effect of eye drops with antioxidants on mild to moderate dry eye symptoms in patients with diabetic retinopathy, evaluating the levels of inflammatory cytokines and oxidative stress in the tear film. The researchers intend to include 78 patients, divided into three intervention groups, who will be randomly assigned an eye drop with antioxidants, where the patient must apply one drop in each eye for 1 month. In the study, the characteristics of the surface of the eye will be evaluated and tear samples will be taken from each eye, before and after the intervention with the eye drops. Subsequently, the clinical and sample results will be evaluated to compare the effects between them.

Conditions

Dry Eye Syndromes; Diabetic Retinopathy; Oxidative Stress; Tear Film Deficiency

Keywords

Dry Eye Disease; Oxidative Stress biomarkers; Inflammatory biomarkers; Tear film; Eye drops; Diabetic Retinopathy

Outcome Measures

Primary Outcomes (6)

• Change from baseline in levels of tumor necrosis factor alpha (TNF-a) in tear film at 30 days.

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  30 days

• Change from baseline in levels of interleukin 8 (IL-8)

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  30 days

• Change from baseline in levels of interleukin 6 (IL-6)

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in pg/mL.

  30 days

• Change from baseline in levels of interleukin 10 (IL-10)

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  30 days

• Changes from baseline in total antioxidant capacity in the tear film at 30 days.

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. Total antioxidant capacity concentration will be determined with colorimetric assay technique and reported in units called Trolox equivalents (TE), nmol/sample.

  30 days

• Change from baseline in lipoperoxides levels in tear film at 30 days.

  Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. Lipoperoxides concentration will be determined with colorimetric assay technique and reported in nmol/mL.

  30 days

Secondary Outcomes (5)

• Change from baseline in the pattern of ocular surface staining with fluorescein sodium according to Oxford Scheme at 30 days.

  30 days

• Change from baseline in the pattern of ocular surface staining with lissamine green according to Oxford Scheme at 30 days.

  30 days

• Change from baseline in the tear break-up time (TBUT) in seconds at 30 days.

  30 days

• Change from baseline in tear film osmolarity at 30 days.

  30 days

• Change from baseline in tear secretion in mm with Schirmer I test at 30 days.

  30 days

Other Outcomes (1)

• Change from baseline severity of dry eye symptoms according the punctuation in Ocular Surface Disease Index (OSDI) at 30 days

  30 days.

Study Arms (3)

Q10 coenzyme, vitamin E and cross-linked hyaluronic acid

EXPERIMENTAL

This arm will administer eye drops with a combination of cross-linked hyaluronic acid, Q10 coenzyme and vitamin E, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.

Drug: VisuXL®

Sodium hyaluronate

ACTIVE COMPARATOR

This arm will administer eye drops with sodium hyaluronate, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.

Drug: Lagricel PF®

Sodium hyaluronate and chondroitin sulfate

ACTIVE COMPARATOR

This arm will administer eye drops with a combination of sodium hyaluronate and chondroitin sulfate, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.

Drug: Humylub PF®

Interventions

VisuXL® DRUG

It consists of a preservative-free eye drop composed of 100 mg cross-linked hyaluronic acid, 100 mg coenzyme Q10, 500 mg vitamin E TPGS (D-alpha-tocopheryl polyethylene glycol succinate), one drop is applied in each eye every 4 hours for a month.

Also known as: VisuXL tear drop

Q10 coenzyme, vitamin E and cross-linked hyaluronic acid

Lagricel PF® DRUG

It consists of a preservative-free eye drop composed of sodium hyaluronate 0.4%, one drop is applied in each eye every 4 hours for a month.

Also known as: Lagricel preservative free

Sodium hyaluronate

Humylub PF® DRUG

It consists of eye drops without preservatives composed of 0.1% sodium hyaluronate and 0.18% chondroitin sulfate, one drop is applied to each eye every 4 hours for a month.

Also known as: Humylub preservative free

Sodium hyaluronate and chondroitin sulfate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 2 diabetes, with presence of diabetic retinopathy in any of its stages without data on severity
• Patients who voluntarily give their informed consent.
• Patients who meet an Ocular Surface Disease Index (OSDI) score between 13-32 points (mild to moderate severity)
• Patients who meet one or more of the following:
• Tear film breakup time equal to or less than 10 seconds
• Corneal fluorescein staining with more than 5 sites
• Conjunctival staining with more than 9 sites.
• Non-smokers or history of inactive smoking \> 6 months
• Metabolic criteria:
• Glycated hemoglobin equal to or less than 9%
• LDL less than or equal to 100 mg/dl
• Triglycerides less than or equal to 180 mg/dl
• Blood pressure less than or equal to 140/80 mm Hg

You may not qualify if:

• Patients with autoimmune diseases and/or Sjögren's disease
• Patients with neurodegenerative processes and/or cancer
• Present aggregate ophthalmological diagnosis of:
• Glaucoma
• Allergic, viral or bacterial conjunctivitis.
• Demodex
• Eye parasitic infections.
• Unresolved eye trauma
• Scarring diseases of the ocular surface
• Corneal or conjunctival ulcers.
• Filamentous keratitis, neurotrophic
• Bullous keratopathy
• Patients taking any of the following medications:
• Osmotic diuretics
• Alpha agonists

Sponsors & Collaborators

• Adolfo Daniel Rodriguez-Carrizalez: lead
• Hospital Civil de Guadalajara: collaborator

Study Sites (1)

Institute of Experimental and Clinical Therapeutics,

Guadalajara, Jalisco, 44340, Mexico

RECRUITING

Related Publications (12)

• 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

• Pastor-Maldonado CJ, Suarez-Rivero JM, Povea-Cabello S, Alvarez-Cordoba M, Villalon-Garcia I, Munuera-Cabeza M, Suarez-Carrillo A, Talaveron-Rey M, Sanchez-Alcazar JA. Coenzyme Q10: Novel Formulations and Medical Trends. Int J Mol Sci. 2020 Nov 10;21(22):8432. doi: 10.3390/ijms21228432.

  PMID: 33182646 BACKGROUND

• Postorino EI, Rania L, Aragona E, Mannucci C, Alibrandi A, Calapai G, Puzzolo D, Aragona P. Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye. Eur J Ophthalmol. 2018 Jan;28(1):25-31. doi: 10.5301/ejo.5001011. Epub 2018 Feb 19.

  PMID: 28777385 BACKGROUND

• Najafi L, Malek M, Valojerdi AE, Aghili R, Khamseh ME, Fallah AE, Tokhmehchi MR, Behrouz MJ. Dry eye and its correlation to diabetes microvascular complications in people with type 2 diabetes mellitus. J Diabetes Complications. 2013 Sep-Oct;27(5):459-62. doi: 10.1016/j.jdiacomp.2013.04.006. Epub 2013 May 30.

  PMID: 23726741 BACKGROUND

• Graue-Hernandez EO, Serna-Ojeda JC, Estrada-Reyes C, Navas A, Arrieta-Camacho J, Jimenez-Corona A. Dry eye symptoms and associated risk factors among adults aged 50 or more years in Central Mexico. Salud Publica Mex. 2018 Sep-Oct;60(5):520-527. doi: 10.21149/9024.

  PMID: 30550113 BACKGROUND

• Gao Y, Zhang Y, Ru YS, Wang XW, Yang JZ, Li CH, Wang HX, Li XR, Li B. Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy. Int J Ophthalmol. 2015 Apr 18;8(2):358-64. doi: 10.3980/j.issn.2222-3959.2015.02.26. eCollection 2015.

  PMID: 25938056 BACKGROUND

• Fong PY, Shih KC, Lam PY, Chan TCY, Jhanji V, Tong L. Role of tear film biomarkers in the diagnosis and management of dry eye disease. Taiwan J Ophthalmol. 2019 Sep 12;9(3):150-159. doi: 10.4103/tjo.tjo_56_19. eCollection 2019 Jul-Sep.

  PMID: 31572651 BACKGROUND

• Seen S, Tong L. Dry eye disease and oxidative stress. Acta Ophthalmol. 2018 Jun;96(4):e412-e420. doi: 10.1111/aos.13526. Epub 2017 Aug 21.

  PMID: 28834388 BACKGROUND

• Dogru M, Kojima T, Simsek C, Tsubota K. Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES163-DES168. doi: 10.1167/iovs.17-23402.

  PMID: 30481822 BACKGROUND

• Navel V, Sapin V, Henrioux F, Blanchon L, Labbe A, Chiambaretta F, Baudouin C, Dutheil F. Oxidative and antioxidative stress markers in dry eye disease: A systematic review and meta-analysis. Acta Ophthalmol. 2022 Feb;100(1):45-57. doi: 10.1111/aos.14892. Epub 2021 May 2.

  PMID: 33938134 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

• 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 RESULT

MeSH Terms

Conditions

Dry Eye Syndromes; Diabetic Retinopathy

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Retinal Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Adolfo D Rodriguez-Carrizalez, M.D/PhD

  University of Guadalajara

  STUDY DIRECTOR

Central Study Contacts

Adolfo D Rodríguez-Carrizalez, M.D./PhD

CONTACT

+52 33 10585200; leinadkit@hotmail.com

María G Martínez-Ruiz, M.D.

CONTACT

+52 33 31874939; maria.mruiz@alumnos.udg.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Clinical trial phase 2 A.

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: June 23, 2022
• Study Start: November 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: January 31, 2024
• Last Updated: June 29, 2022

Record last verified: 2022-06

Locations

ME (1)