Tear Film Markers in Dry Eye Syndrome

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ClinicalTrials.gov Identifier: NCT04515329

Recruitment Status : Not yet recruiting

First Posted : August 17, 2020

Last Update Posted : January 8, 2021

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Sponsor:

Collaborator:

Sun Pharma Global FZE

Information provided by (Responsible Party):

Vishal Jhanji, University of Pittsburgh

Study Description

Brief Summary:

Dry eye is the most common reason for visit to an ophthalmologist's office. The prevalence is on the rise and is mainly attributed to factors such as increased environmental pollution and contact lens use. The current management options are limited to over the counter artificial tear drops and three FDA-approved drugs. Of these, cyclosporine has been used worldwide for treating mild to moderate dry eyes. The earlier version consisted of 0.05% cyclosporine which worked well for a limited number of inflammatory dry eye conditions. Recently, 0.09% cyclosporine was approved by the FDA. The nearly double concentration is expected to be more beneficial for severe inflammation which is often seen in Sjögren syndrome and other Rheumatological conditions associated with dry eyes. In this pilot project, the investigator proposes to evaluate the change in expression of SLURP1 and other markers of ocular surface inflammation before and after treatment with 0.09% cyclosporine eye drops.

Condition or disease	Intervention/treatment	Phase
Dry Eye	Drug: Cyclosporine Drug: Artificial tear	Phase 4

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Detailed Description:

Subjects will be recruited based on their diagnosis of dry eyes and an estimate of the severity of the disease that would be made by the investigator based on the patient's history and clinical examination.

Dry Eye Severity is determined by scoring > 12 on the Ocular Surface Disease Index (OSDI) rubric, which is standard practice.

Patients who have been diagnosed with dry eye, but who have not been prescribed a drug to treat that condition, will be recruited.

After signing a consent form, subjects will complete their routine care eye exam.

The PI will include consecutive patients for each arm. Once the mandate is completed in both arms, the investigator will stop the recruitment. The investigator will include patients who will choose to use artificial tear drops in one group. For the other group, the investigator will choose patients who would electively agree to use cyclosporine eyedrops. If these patients choose not to be a part of the study, they will still end up using the treatment that they would like to use.

Study arm: Treatment will be commenced with cyclosporine eye drops twice daily with preservative-free artificial tear drops 4 times a day (Treatment).
Control arm: Preservative-free artificial tear drops 4 times a day (Control).

Eye drop timetable:

If instructed to take 4 times a day, the subject will instill one drop in the morning, the afternoon, the early evening, and before bedtime.
If instructed to take 2 times a day, the subject will instill one drop in the morning and the evening.
Subjects will also be instructed to space eye drops by 3-5 minutes.

Both the Cyclosporine and Artificial Tears will be ordered by the subject's doctor, which will be available through the subject's pharmacist. These drops are normally prescribed as part of the subject's routine care.

Both subjects and physicians will be aware of the type of treatment; however the data entry and analysis would be blinded. This will be done by giving each individual subject a linking code.

Subjects will self-administer the eyedrops for 8 weeks.

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Research Procedures:

The following samples would be collected at baseline and at Week 8:

Baseline (Visit 1):

Randomization
Tear Fluid Collection
Impression Cytology

Week 4 (Visit 2):

• Data collection: Subject will follow up normally with their ophthalmologist as part of their routine care eye exam. The following will be collected: Demographics; Clinical History and office visits; Images and Photography; and Microbiology records.

Week 8 (Visit 3):

Tear Fluid Collection
Impression Cytology

Visits 1 and 3 will add up to 20 minutes to the participant's routine care eye exam.

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Explanation of Procedures:

Numbing Anesthesia Drop (Proparacaine 0.5%):

Subject will receive a numbing anesthesia drop (Proparacaine 0.5%) in the eye that is inflamed as part of their standard of care. The effect of this drop will wear off in 20 minutes after instillation, but the subject is not required to stay until the numbing subsides.

Tear Fluid Collection (Schirmer Testing):

A small amount of the subject's tears will be collected by placing paper strips in the corner of their eye.

Impression Cytology:

The investigators will collect a single sample of material from the surface of the subject's eye and then evaluate it on a cellular level. During impression cytology the subject will be asked to look straight ahead with their chin slightly lifted. A drop of anesthetic eye drops is instilled in the lower fornix of the eye. The plunger of the impression cytology device (EYEPRIM; OPIA Technologies SAS, Paris, France, or equivalent) is pushed to touch the cornea with the membrane gently for 5 seconds. The pressure is released before removing the device. The membrane is then carefully transferred from the device into a 1.5-mL tube using a pair of sterile forceps. Multiple EYEPRIM membranes may be collected. One drop of artificial tear drop would be instilled on the surface of the eye. The participant would be asked to close his/her eye for a few seconds. A capillary tube or Schirmer's strip would be used to collect the tear film.

The total duration of research procedures will be approximately 20 minutes.

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Samples:

Microbiology analysis will be processed at the UPMC Eye Center's Ophthalmology Microbiology Lab.

The tear fluid samples would be analyzed by ELISA for:

Matrix metalloproteinase-9
SLURP-1
HLA-DR5
IL-1RA,
IL-6, and
IL-8

Impression cytology samples would be used to isolate total RNA, which will be converted to cDNA and used for QPCR evaluation of corresponding transcripts for the above targets. QPCRs along with ELISAs would provide convincing evidence to elucidate the effect(s) of 0.09% cyclosporine on expression of these markers of ocular surface inflammation. At the end of the study, the subject assignments will be unmasked and the difference between the treatment and the control groups analyzed.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Study arm: Treatment will be commenced with cyclosporine eye drops twice daily with preservative-free artificial tear drops 4 times a day (Treatment). Control arm: Preservative-free artificial tear drops 4 times a day (Control).
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Tear Film Markers in Dry Eye Syndrome: Impact of Immunomodulatory Therapy
Estimated Study Start Date :	March 2021
Estimated Primary Completion Date :	January 3, 2023
Estimated Study Completion Date :	January 3, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tears

Drug Information available for: Hydroxypropyl methylcellulose Cyclosporine

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cyclosporine + Artificial Tears Cyclosporine eye drops twice daily (Treatment) with preservative-free artificial tear drops 4 times a day (Control).	Drug: Cyclosporine Eye drops taken twice daily. Other Name: Cequa Drug: Artificial tear Preservative-free artificial tear drops 4 times a day. Other Name: Preservative-free artificial tears
Artificial Tears Preservative-free artificial tear drops 4 times a day (Control).	Drug: Artificial tear Preservative-free artificial tear drops 4 times a day. Other Name: Preservative-free artificial tears

Outcome Measures

Primary Outcome Measures :

Tear Film Cytokines [ Time Frame: At the time of sample collection (Baseline and Month 6). ]
Change from Baseline in tear film cytokines at 6 months. The tear fluid samples would be analyzed by ELISA for: Matrix metalloproteinase-9; SLURP-1; HLA-DR5; IL-1RA; IL-6; and IL-8.

Secondary Outcome Measures :

OSDI Score [ Time Frame: Last follow-up (Month 6). ]
Change is Ocular Surface Disease Index (OSDI) score at Month 6.

The OSDI quickly assesses the symptoms of ocular irritation in dry eye disease and how they affect functioning related to vision. This 12-item questionnaire assesses dry eye symptoms and the effects it has on vision-related function in the past week of the patient's life. The questionnaire has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on a 0 to 4 scale with 0 corresponding to "none of the time" and 4 corresponding to "all of the time." A final score is calculated which ranges from 0 to 100 with scores 0 to 12 representing normal, 13 to 22 representing mild dry eye disease, 23 to 32 representing moderate dry eye disease, and greater than 33 representing severe dry eye disease.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosed with Dry Eye, but who have not been prescribed a drug to treat this condition.
18 years of age and older
OSDI score > 12

Exclusion Criteria:

Younger than 18 years of age.
Any other associated eye diseases other than Dry Eye.
Inability to understand and give informed consent.
Patients diagnosed with Dry Eye who are already using Cequa.

Contacts and Locations

Information from the National Library of Medicine

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): NCT04515329

Contacts

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Contact: Michael J DeRosa, BS, BA	412-647-3343	derosamj@upmc.edu
Contact: Rose Carla Aubourg, BA	412-647-3373	aubourgrc@upmc.edu

Locations

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United States, Pennsylvania
UPMC Eye Center
Pittsburgh, Pennsylvania, United States, 15213
Contact: Michael J DeRosa, BS; BA 412-647-3343 derosamj@upmc.edu
Contact: Rose Carla Aubourg, BA 412-647-3373 aubourgrc@upmc.edu
Principal Investigator: Vishal Jhanji, MD

Sponsors and Collaborators

Vishal Jhanji

Sun Pharma Global FZE

Investigators

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Principal Investigator:	Vishal Jhanji, MD	UPMC Eye Center

More Information

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Responsible Party:	Vishal Jhanji, Professor - Cornea Service, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT04515329
Other Study ID Numbers:	STUDY20010206
First Posted:	August 17, 2020 Key Record Dates
Last Update Posted:	January 8, 2021
Last Verified:	November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Additional relevant MeSH terms:

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Keratoconjunctivitis Sicca Dry Eye Syndromes Keratoconjunctivitis Conjunctivitis Conjunctival Diseases Eye Diseases Keratitis Corneal Diseases Lacrimal Apparatus Diseases Cyclosporine Lubricant Eye Drops Cyclosporins	Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Dermatologic Agents Antirheumatic Agents Calcineurin Inhibitors Ophthalmic Solutions Pharmaceutical Solutions

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