The Effects of Cyclosporin A in a Low Humidity Environment, on the Ocular Surface (CsA)

The Effects of Cyclosporin A Emulsion, (Restasis), on the Ocular Surface in Response to Low Humidity Environment in Patients With Dry Eye

This study will test that hypothesis that topical administration of the FDA approved immunomodulatory agent cyclosporin A emulsion will minimize irritation and ocular surface disease that results from a short term low humidity environmental stress

Study Overview

• Status: Terminated
• Conditions: Dry Eye
• Intervention / Treatment: Drug: Cyclosporin 0.05% emulsion; Drug: Endura, Refresh artificial tears

Detailed Description

This is a pilot study designed to evaluate the effect of two conventional dry eye therapies, artificial tears to hydrate and cyclosporine A as an anti-inflammatory, on the irritation symptoms and ocular surface disease of dry eye patients who will be exposed to a low humidity environment for 90 minutes. Patients with dry eye will be enrolled in this study and complete a validated symptom questionnaire and then undergo a complete ocular surface and tear examination to characterize their disease. Enrolled subjects will be exposed to a low humidity environment at the initial evaluation prior to any treatment and will be exposed to a low humidity environment for a second time. They will be randomized to receive either artificial tears or 0.05% cyclosporine A emulsion drop four times a day for 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Alkek Eye Center, Dept of Ophthalmology, Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signature on the written informed consent form
• Patient willingness and ability to return for all visits during the study
• Rapid tear film break up time of seven seconds or less in at least one eye AND
• Both cornea fluorescein staining score greater than or equal to 3 and conjunctival lissamine green staining greater than or equal to 3 in at least one eye
• Ocular Surface Disease Index Symptom Severity score of twenty or greater
• Tear meniscus height less than or equal to 230um
• Intact corneal sensitivity
• Willingness to discontinue use of any current dry eye treatment (except artificial tears) for four weeks prior to enrollment, and during the course of the study

Exclusion Criteria:

• Compromised cognitive ability which may be expected to interfere with study compliance
• Uncontrolled or poorly controlled diabetes or heart or pulmonary disease that could, in the judgment of the investigator, jeopardize subject safety or interfere with the interpretation of the results of the study
• Known hypersensitivity to any components of the artificial tears or cyclosporin A eye drops Anticipated contact lens wear during the study
• History of corneal transplant
• Active ocular infection, uveitis or non-KCS related inflammation
• History of cataract surgery within 3 months prior to enrollment
• History of pterygium removal within 6 months prior to enrollment
• Reduced corneal sensitivity
• Initiation, discontinuation or change in dosage of hormone replacement therapy (HRT), fish oil, evening primrose, flaxseed, or black current seed oil supplements, antihistamines, cholinergic agents, beta-blocking agents, tricyclic or SSRI antidepressants, phenothiazines, or topical or systemic acne rosacea medications in two months prior to enrollment, or anticipated change in dosage during course of study
• Topical ophthalmic medications within prior 4 weeks, or anticipated use of same during the study (except artificial tears)
• Occlusion of the lacrimal puncta either surgically or with temporary collagen punctal plugs within three months prior to study, or anticipated use of same during study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporin 0.05% emulsion; used in the eye 4 times a day	Drug: Cyclosporin 0.05% emulsion; Topical therapy for dry eye; Other Names: Artificial tears; Cyclosporin 0.05% emulsion (Restasis); Dry Eyes
Active Comparator: Endura Refresh, Artificial Tears; Over the Counter artificial tears used in the eye 4 times a day	Drug: Endura, Refresh artificial tears; Over the counter therapy for dry eye, used 4 times a day; Other Names: Artificial Tears; Dry Eyes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Fluorescein Staining	The mean difference in corneal staining using the adjusted CCLR global staining score before and after the environmental challenge at visits baseline and Visit 3/Day 42 when patients were subjected to a 90-minute low humidity stress. Corneal fluorescein staining was graded 0-100 in 5 zones on the cornea. The scores ranged from 0 (minimum) to 500 (maximum). A higher score indicates there was greater cornea disease induced by the low humidity stress on Day 42	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eye Irritation Symptoms	The mean difference in subject's scoring of eye irritation symptoms using a VAS (visual analog scale) questionnaire before and after the environmental challenge after treatment at Visit 3/Day 42 when patients were subjected to a 90-minute low humidity stress. Symptoms were graded on a 4 question VAS 0-5 for each question, with scores summed for all questions for a total score that ranges from 0 (minimum) to 20 (maximum) for the pre and post challenge questionnaires. The outcome measure is the difference in the post to pre total score ranging from -20 (maximum improvement) to 20 (maximum worsening). A minus difference indicated the subject had lower irritation symptoms following the lower humidity challenge, while a positive difference indicated the subject had greater irritation following the low humidity challenge on Day 42.	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival Goblet Cells	The number of conjunctival goblet cells measured in impression cytology at screening/baseline before and after low humidity exposure at the baseline and Day 42 visits. No (zero) subjects were analyzed because the assay was not performed and data was not collected because the study was terminated due to loss of funding.	6 weeks

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Allergan
• Investigators: Principal Investigator: Stephen C. Pflugfelder, MD, Baylor College of Medicine, Department of Ophthalmology

Publications and helpful links

General Publications

• Alex A, Edwards A, Hays JD, Kerkstra M, Shih A, de Paiva CS, Pflugfelder SC. Factors predicting the ocular surface response to desiccating environmental stress. Invest Ophthalmol Vis Sci. 2013 May 7;54(5):3325-32. doi: 10.1167/iovs.12-11322.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 16, 2014
• First Submitted That Met QC Criteria: July 23, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Dry eye; cyclosporin; Restasis; artificial tears; environmental stress
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Pharmaceutical Solutions; Calcineurin Inhibitors; Ophthalmic Solutions; Cyclosporine; Cyclosporins; Lubricant Eye Drops
• Other Study ID Numbers: H-33276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study was terminated early because of loss of funding.