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

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02199964
• Collaborator: Allergan (Industry)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: Cyclosporin 0.05% emulsion; Drug: Endura, Refresh artificial tears	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: The Effects of Cyclosporin A Emulsion, (Restasis), on the Ocular Surface in Response to Low Humidity Environment in Patients With Dry Eye
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

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: Dry Eyes Artificial Tears

Outcome Measures

Primary Outcome Measures

1. Corneal Fluorescein Staining [6 weeks]

   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

Secondary Outcome Measures

1. Eye Irritation Symptoms [6 weeks]

   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.

Other Outcome Measures

1. Conjunctival Goblet Cells [6 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkek Eye Center, Dept of Ophthalmology, Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine
• Allergan

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Steven Pflugfelder, Director of Ocular Surface Clinical Trials, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT02199964
• Other Study ID Numbers: H-33276
• First Posted: Jul 25, 2014
• Last Update Posted: Feb 20, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Steven Pflugfelder, Director of Ocular Surface Clinical Trials, Baylor College of Medicine: Dry eye; environmental stress; artificial tears; cyclosporin; Restasis
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Cyclosporine; Lubricant Eye Drops; Cyclosporins

Study Results

Participant Flow

Recruitment Details	Recruitment process occurred at the medical clinic of the primary investigator. Recruitment began July 2014 and ended December 2015.
Pre-assignment Detail	There were no pre-assignment details.

Arm/Group Title	Cyclosporin 0.05% Emulsion	Endura Refresh, Artificial Tears
Arm/Group Description	used in the eye 4 times a day Cyclosporin 0.05% emulsion: Topical therapy for dry eye	Over the Counter artificial tears used in the eye 4 times a day Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cyclosporin 0.05% Emulsion	Endura Refresh, Artificial Tears	Total
Arm/Group Description	used in the eye 4 times a day Cyclosporin 0.05% emulsion: Topical therapy for dry eye	Over the Counter artificial tears used in the eye 4 times a day Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day	Total of all reporting groups
Overall Participants	2	2	4
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	2 100%	4 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (9.9)	58 (4.2)	54.5 (7.4)
Sex: Female, Male (Count of Participants)
Female	2 100%	2 100%	4 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Corneal Fluorescein Staining
Description	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
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Due to loss of funding, this study was not completed and enrollment ended. Data from only 2 subjects per group was analyzed

Arm/Group Title	Cyclosporin 0.05% Emulsion	Endura Refresh, Artificial Tears
Arm/Group Description	used in the eye 4 times a day Cyclosporin 0.05% emulsion: Topical therapy for dry eye	Over the Counter artificial tears used in the eye 4 times a day Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day
Measure Participants	2	2
Mean (Standard Deviation) [units on a scale]	21.5 (13.44)	29 (15.6)

2. Secondary Outcome

Title	Eye Irritation Symptoms
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyclosporin 0.05% Emulsion	Endura Refresh, Artificial Tears
Arm/Group Description	used in the eye 4 times a day Cyclosporin 0.05% emulsion: Topical therapy for dry eye	Over the Counter artificial tears used in the eye 4 times a day Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day
Measure Participants	2	2
Mean (Standard Deviation) [units on a scale]	1.5 (2.1)	1 (0)

3. Other Pre-specified Outcome

Title	Conjunctival Goblet Cells
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse event data was collected up to 6 months until study termination.
Adverse Event Reporting Description	Adverse event collection was done at each subject visit.
Arm/Group Title	Cyclosporin 0.05% Emulsion		Endura Refresh, Artificial Tears
Arm/Group Description	used in the eye 4 times a day Cyclosporin 0.05% emulsion: Topical therapy for dry eye		Over the Counter artificial tears used in the eye 4 times a day Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day
All Cause Mortality
	Cyclosporin 0.05% Emulsion		Endura Refresh, Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Cyclosporin 0.05% Emulsion		Endura Refresh, Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Cyclosporin 0.05% Emulsion		Endura Refresh, Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.