Cross-linked Hyaluronic Acid and Coenzyme Q10 in the Treatment of Dry Eye (DEDCO)

March 8, 2017 updated by: Pasquale Aragona, Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Study on the Effectiveness of Eye-drops Containing Cross-linked Hyaluronic Acid and Coenzyme Q10 in the Treatment of Patients With Mild to Moderate Dry Eye

Background: Dry eye disease (DED) is a common condition causing burden on visual function and reducing quality of life. Corticosteroids and/or cyclosporine eye drops are able to improve DED symptoms, however, side effects of immune suppression and cost lead patients often to suspend treatment. Consequently, is important to identify therapies alleviating DED symptoms. A randomized, controlled, single masked study, was performed in 40 patients affected by mild to moderate DED, to evaluate efficacy and safety of a collyrium based on cross-linked hyaluronic acid (XLHA) added with Coenzyme Q10 (CoQ10) in comparison to an eye drop considered a gold standard for tear substitutes, based on hyaluronic acid (HA) 0.15%.

Methods: eye drops were administered four times a day for 90 days to enrolled subjects divided in two groups: group A treated with XLHA+CoQ10, group B treated with HA. Ocular Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular pressure (IOP), fundus exam, tear break-up time (TBUT), corneal and conjunctival fluorescein staining, corneal esthesiometry, corneal confocal microscopy, were performed at different visits until the 90th day.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction:

Dry eye disease (DED) is a common eye condition causing burden on visual function and reducing quality of life and work productivity. DED is a tear film disorder resulting in hyperosmolarity of tear film and inflammation of ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. This condition provokes traumatisms caused by the movement of the eyelids on the ocular surface and an insufficient cleansing of the same by microbial agents and/or foreign bodies.

Prevalence of DED increases with age and women are particularly susceptible, especially those receiving estrogens. The pathogenesis is not fully understood; however, it has been recognized that inflammation has a prominent role .

The most common symptoms of DED are: burning, foreign body sensation in the eye, difficulty in opening the eyelids on awakening, blurred vision and, in severe cases, pain and photophobia. DED is accompanied by increased tear film osmolarity and inflammation of ocular surface.

There is no gold standard treatment for DED, but corticosteroids and/or cyclosporine eye drops improve the symptoms. However, given the side effects of immune suppression and the cost of pharmaceutical preparations, patients often suspend treatment before the effectiveness of therapy can be verified.

Artificial tears are considered a mainstay in dry eye treatment. Hyaluronic acid (HA), a natural glycosaminoglycan, is a component of tear film. It increases tear film viscosity and hydrates and lubricates the ocular surface. HA possesses intrinsic water retention properties, viscoelasticity and favours the healing of corneal and conjunctival epithelium. Safety and efficacy of HA for the treatment of DED has been demonstrated. Eye-drops containing HA determine a reduction of ocular surface inflammation, with consequent improvement of quality of corneal and conjunctival epithelium. Our previous clinical study showed HA beneficial effects on the conjunctival epithelium of dry eye patients. Results of another clinical trial, confirm beneficial effects of HA and show that in combination with tamarind seed polysaccharide it can be effective in improving dry eye symptoms, opening new scenarios in the treatment of this disease by combining different molecules.

Coenzyme Q10 (CoQ10) is an endogenous, lipid soluble molecule, also known as ubiquinone. CoQ10 plays a key role in oxidative metabolism supporting the adenosine triphosphate (ATP) in the mitochondria and, in its reduced form, acts as a lipid antioxidant. In almost all tissues of the human body, CoQ10 levels decline with age and ocular function is sensitive to variations of concentration of CoQ10 .

A randomized, controlled, single masked study, was performed in mild to moderate dry eye patients, to evaluate the efficacy and the safety of a collyrium based on cross-linked HA (XLHA) added with CoQ10 in comparison to an eye drop formulation, commonly used in clinical practice and considered a gold standard for tear substitutes, in the treatment of dry eye, based on 0.15% linear HA.

Methods This randomised, single-masked, parallel-group comparative study investigated the efficacy and safety, in treatment of dry eye patients, of an ophthalmic solution containing XLHA added with CoQ10 (VisuXL®, Visufarma, Rome, Italy) in comparison with a formulation containing hyaluronic acid 0.15% (HA). The study screened 46 patients and 40 were enrolled [(13 male, 17 female, with an age range 40-79 years; mean age 62 ± 12.8 (SD) years)] suffering from mild to moderate dry eye attending to the Eye Clinic, Department of Biomedical Sciences, Regional Referral Center for the Ocular Surface Diseases, University of Messina, Messina, Italy. Enrolled subjects were divided into two treatment groups (Group A receiving the study formulation based on XLHA+CoQ10 and Group B receiving the comparator formulation based on 0.15% HA) according to a randomization scheme, corresponding to allocation codes generated for the two treatments using the permuted block method. The two eye-drops compositions used for the study were the following: group A formulation (XLHA+CoQ10): 100 ml containing Cross-Linked HA sodium salt 100 mg, Coenzyme Q10 100 mg, with Vitamin E tocopheryl polyethylene glycol succinate (TPGS) 500 mg (as a solubilizing agent for the lipid soluble CoQ10), Isotonic buffered solution q.s. to 100 ml; group B formulation: HA sodium salt 100 mg; isotonic buffered solution q.s. to 100 ml. Both formulations were unpreserved.

All patients included were treated for a run-in period of 7 days with one eye drop of saline four times daily. At the end of this period (time 0 of the study) the subjects were randomly divided into the two groups and assigned to a treatment.

The visits were carried out in a blind fashion by investigators. Eye drops were administered four times a day for 12 weeks and subjects enrolled in the study underwent grading of subjective symptoms and clinical examination at time 0 and after 15, 30, and 90 days. The patients were allowed to know the brand name of the eye drops they were using.

Outcomes The Ocular Surface Disease Index (OSDI) questionnaire, visual acuity, intraocular pressure (IOP), and fundus exam, tear break-up time (TBUT), corneal and conjunctival fluorescein staining, esthesiometry, corneal confocal microscopy. Adverse events were monitored.

OSDI is one of the most widely used questionnaires. The 12-item OSDI questionnaire scores range from 0 to 100, high scores represent higher disability. The scale showed good sensitivity in discriminating normal people from subjects affected by dry eye and to correlate well with disease severity.

The ocular surface fluorescein stain score was assessed 3 minutes after the instillation of fluorescein; a modified Oxford score was used: cornea and conjunctiva were scored separately from 0 to 5 (from 0 = none to 5 = extended areas of confluent stain), for the conjunctiva a mean for the scores from the nasal and temporal regions was used. The ocular surface was observed through a cobalt blue light and a Wratten #12 yellow filter.The difference among the scores obtained in each visit was calculated.

Corneal sensitivity was measured by Cochet-Bonnet aesthesiometer to evaluate the activity of the ophthalmic branch of fifth cranial nerve (trigeminal). It was measured by the evaluating the length of the filament able to evoke a tactile sensation (mm of filament).

In vivo confocal microscopy was performed, after the topical instillation of a drop of unpreserved 0.4% oxybuprocaine, using the 40x contact objective and the additional Z-Ring probe, to allow a precise positioning of the probe over the central corneal area.

For statistical analysis, only the results of right eyes were considered. Student's t-test and Mann-Whitney U-test were used as appropriate. Values of P≤0.05 were considered statistically significant.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age between 18 and 80 years,
  • history of at least 3 months of dry eye symptoms referable to mild to moderate dry eye.

Exclusion Criteria:

  • presence of any ocular disease, present or past, other than dry eye;
  • previous ocular surgery,
  • use of contact lens or topic treatments other than tear substitutes;
  • presence of systemic diseases requiring a treatment with systemic drugs potentially interfering with tear productions;
  • hypersensitivity to the active substance or to excipients;
  • participation in a clinical trial during the 3 months prior to the beginning of the study,
  • pregnancy or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XLHA+CoQ10
XLHA+CoQ10 eye drop administered four times a day for 12 weeks (90 days).
Device: XLHA+CoQ10
XLHA+CoQ10 for four times a day for 12 weeks.
Other Names:
  • VisuXL®
Active Comparator: Hyaluronic acid (HA)
Hyaluronic acid (HA) eye drop administered four times a day for 12 weeks (90 days).
Device: Hyaluronic acid (HA)
Hyaluronic acid (HA) for four times a day for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular Surface Disease Index (OSDI) questionnaire.
Time Frame: Up to 90 days.
The OSDI is assessed on a scale of 0 to 100, with higher scores representing greater disability. OSDI is a valid and reliable instrument for measuring dry eye disease (normal, mild to moderate, and severe) and effect on vision-related function. OSDI demonstrates sensitivity and specificity in distinguishing between normal subjects and patients with dry eye disease.
Up to 90 days.
Corneal and conjunctival staining.
Time Frame: Up to 90 days.
Corneal and conjunctival staining of the ocular surface after instillation of vital dyes was developed to quantify epithelial surface damage in dry eye patients. Ocular surface fluorescein stain score was assessed 3 minutes after the instillation of fluorescein; a modified Oxford score was used: cornea and conjunctiva were scored separately from 0 to 5 (from 0 = none to 5 = extended areas of confluent stain), for the conjunctiva a mean for the scores from the nasal and temporal regions was used. The ocular surface was observed through a cobalt blue light and a Wratten #12 yellow filter.The difference among the scores obtained in each visit was calculated.
Up to 90 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual acuity,
Time Frame: Up to 90 days.
Visual acuity refers to the ability to discern fine distinctions in the environment.
Up to 90 days.
Intraocular pressure (IOP).
Time Frame: Up to 90 days.
IOP = eye fluid pressure measured by tonometry.
Up to 90 days.
Fundus exam.
Time Frame: Up to 90 days.
Fundus exam is observed after use of mydriatic drops enlarging the pupil.
Up to 90 days.
Tear break-up time (TBUT).
Time Frame: Up to 90 days.
Tear breakup time (TBUT) is a test used to assess for evaporative dry eye disease. To measure TBUT, fluorescein is instilled into the patient's tear film then and the patient is asked not to blink while the tear film is observed under cobalt blue illumination. TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film, as seen in this progression of these slit lamps photos over time. A TBUT under 10 seconds is considered abnormal.
Up to 90 days.
Corneal esthesiometry.
Time Frame: Up to 90 days.
Esthesiometry measures sensation, specifically tactile.
Up to 90 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Investigators

  • Principal Investigator: Pasquale Aragona, MD, Azienda Ospedaliera Universitaria Policlinico "G. Martino", Messina, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

February 28, 2017

First Submitted That Met QC Criteria

March 7, 2017

First Posted (Actual)

March 8, 2017

Study Record Updates

Last Update Posted (Actual)

March 10, 2017

Last Update Submitted That Met QC Criteria

March 8, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOUGMartino

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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