Clinical trial NCT03074344: Cross-linked Hyaluronic Acid and Coenzyme Q10 in the Treatment of Dry Eye
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dry Eye Syndrome
Keywords: Dry Eye Syndrome
artificial tear
CoQ10
Hyaluronic acid
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
Sponsor class: OTHER
First posted: 2017-03-08
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, single-masked, parallel-group comparative study.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ocular Surface Disease Index (OSDI) questionnaire.
timeFrame: Up to 90 days.
measure: Corneal and conjunctival staining.
timeFrame: Up to 90 days.
Secondary outcomes:
measure: Visual acuity,
timeFrame: Up to 90 days.
measure: Intraocular pressure (IOP).
timeFrame: Up to 90 days.
measure: Fundus exam.
timeFrame: Up to 90 days.
measure: Tear break-up time (TBUT).
timeFrame: Up to 90 days.
measure: Corneal esthesiometry.
timeFrame: Up to 90 days.
Other outcomes:
Locations:
Study officials:
affiliation: Azienda Ospedaliera Universitaria Policlinico "G. Martino", Messina, Italy
name: Pasquale Aragona, MD
role: PRINCIPAL_INVESTIGATOR
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