Effect of Topical Antioxidants in Dry Eye Disease and Diabetic Retinopathy

NCT ID: NCT05429229

Last Updated: 2022-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-01

Study Completion Date

2024-01-31

Brief Summary

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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.

Detailed Description

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Dry eye syndrome is a multifactorial disease where tear film homeostasis is lost, accompanied by ocular symptoms such as burning, blurred vision, foreign body sensation, ocular redness, itching, in which tear film instability and hyperosmolarity, causing inflammation of the ocular surface, endothelial damage and neurosensory alterations.

Worldwide, in patients with diabetic retinopathy it has a prevalence of 54%, however in Mexico, only a prevalence of 41% has been described in the diabetic population, without having reports of prevalence in patients with diabetic retinopathy.

The state of chronic hyperglycemia in diabetes mellitus causes neuropathic corneal damage and dysfunction of the meibomian glands, this promotes a decrease in tear production, establishing dysfunction of the tear film and a state of hyperosmolarity in it, the latter induces activation of inflammatory mediators and release of proinflammatory cytokines that generate more damage to the corneal surface, entering a vicious cycle of tear film instability.

Likewise, the preexisting state of oxidative stress in patients with diabetic retinopathy, where there is an imbalance between the production and degradation of reactive oxygen species, contributes to the induction of changes in the corneal surface and tear film dysfunction.

Dry eye treatment is focused on the characteristics of the tear film and the characteristics of the ocular surface, with the aim of controlling and improving symptoms, with the use of different formulations and tolerability profiles. However, these are not adequate to reduce the effect of the inflammatory state and oxidative stress present in the tear film and the ocular surface, causing the patient's visual quality to worsen.

The researchers intend to assess whether antioxidant therapy in eye drops influences levels of oxidative stress and inflammatory markers in the tear film.

Conditions

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Dry Eye Syndromes Diabetic Retinopathy Oxidative Stress Tear Film Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Clinical trial phase 2 A.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
Double

Study Groups

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Q10 coenzyme, vitamin E and cross-linked hyaluronic acid

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.

Group Type EXPERIMENTAL

VisuXL®

Intervention Type 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.

Sodium hyaluronate

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.

Group Type ACTIVE_COMPARATOR

Lagricel PF®

Intervention Type 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.

Sodium hyaluronate and chondroitin sulfate

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.

Group Type ACTIVE_COMPARATOR

Humylub PF®

Intervention Type 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.

Interventions

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VisuXL®

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.

Intervention Type DRUG

Lagricel PF®

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.

Intervention Type DRUG

Humylub PF®

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.

Intervention Type DRUG

Other Intervention Names

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VisuXL tear drop Lagricel preservative free Humylub preservative free

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* NSAIDs, cannabinoids or opioids
* Benzodiazepines, selective serotonin reputate inhibitors, monoamine oxidate inhibitors
* nonlepromatous, antimalarials (Chloroquine / Hydroxychloroquine)
* Corticosteroids
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Civil de Guadalajara

OTHER

Sponsor Role collaborator

Adolfo Daniel Rodriguez-Carrizalez

OTHER

Sponsor Role lead

Responsible Party

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Adolfo Daniel Rodriguez-Carrizalez

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Adolfo D Rodriguez-Carrizalez, M.D/PhD

Role: STUDY_DIRECTOR

University of Guadalajara

Locations

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Institute of Experimental and Clinical Therapeutics,

Guadalajara, Jalisco, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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

Role: CONTACT

+52 33 10585200

María G Martínez-Ruiz, M.D.

Role: CONTACT

+52 33 31874939

Facility Contacts

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Adolfo D. Rodriguez-Carrizalez, PhD

Role: primary

+52 33 10585200 ext. 33658

Maria G Martinez-Ruiz, MD

Role: backup

+52 33 31874939

References

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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.

Reference Type BACKGROUND
PMID: 32962301 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33182646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28777385 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23726741 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30550113 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25938056 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31572651 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28834388 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30481822 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33938134 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26321469 (View on PubMed)

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.

Reference Type RESULT
PMID: 23875878 (View on PubMed)

Other Identifiers

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OSRD-20200831-1

Identifier Type: -

Identifier Source: org_study_id

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