Comparing Effect of Topical Tacrolimus 0.03% Versus Cyclosporine 0.05% in Dry Eyes of Secondary Sjogren Syndrome

Sponsor

Pavly Moawd (Other)

Overall Status

Completed

CT.gov ID

NCT03865888

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluation of the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops in treatment of dry eye in Secondary Sjogren Syndrome.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Sjogren Syndrome	Drug: Cyclosporins Drug: Tacrolimus	Phase 3

Detailed Description

Sjogren syndrome is a chronic autoimmune disorder characterized by immune cell infiltration of exocrine glands (exocrinopathy or epitheliitis) and systemic complications due to autoantibody production, immune complex deposition and lymphocytic infiltration of many organs .The loss of aqueous tear flow in Sjogren syndrome is a result of inflammatory cell infiltration of the lacrimal glands.The principal ocular manifestation of which is decreased tear production leading to chronic irritation and damage to the corneal and conjunctival epithelium. Dry eye associated with Sjogren syndrome (SS dry eye) is often more severe than non-Sjogren dry eye (non-SS dry eye). Rose bengal staining, fluorescein staining, impression cytology, and brush cytology show greater changes in SS dry eye owing to a lack of both basic tearing and reflex tearing resulting from lacrimal gland destruction, which is the hallmark of deteriorating clinical conditions.

The initial tear film ocular surface society dry eye workshop report noted the importance of ocular surface inflammation not only in the development of, but as a downstream effect and propagator of dry eye disease , and reviewed a range of therapies that function, at least in part, by anti-inflammatory mechanisms of action. Thus understanding the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday practice.

Cyclosporine is understood to be an immunomodulatory drug with anti-inflammatory properties, as well as having other actions relevant to managing dry eye disease . Topical cyclosporine was approved by the FDA for the treatment of moderate-to-severe dry eye disease in 2003, based on an improvement in tear production.

Tacrolimus, a macrolide produced by Streptomyces tsukubaensis,was discovered in 1984 in Japan while searching for new immunosuppressive and cancer chemotherapeutic agents. The use of tacrolimus is of special interest in ophthalmology because it is indicated to be effective in the treatment of immune-mediated diseases Thus, the investigators performed this study to evaluate the effect of two different immunomodulatory eye drops on the ocular surface which are topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops in treatment of dry eye in Secondary Sjogren Syndrome.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Evaluation of the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops in treatment of dry eye in Secondary Sjogren Syndrome.Evaluation of the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops in treatment of dry eye in Secondary Sjogren Syndrome.

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Effect of Topical Application of Tacrolimus 0.03% (FK506) Eye Drops Versus Cyclosporine 0.05% Eye Drops in Treatment of Dry Eye in Secondary Sjogren Syndrome

Actual Study Start Date :

Oct 30, 2018

Actual Primary Completion Date :

Feb 1, 2019

Actual Study Completion Date :

Apr 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cyclosporins 0.05 % treated eyes Topical Cyclosporins 0.05% eye drops twice in one eye for 3 months	Drug: Cyclosporins Cyclosporins eye drops to be administered in dry eyes Other Names: Restasis
Active Comparator: Tacrolimus 0.03% treated eyes Topical Tacrolimus 0.03% eye drops twice in one eye for 3 months	Drug: Tacrolimus Tacrolimus eye drops to be administered in dry eyes Other Names: FK506

Arm

Intervention/Treatment

Active Comparator: Cyclosporins 0.05 % treated eyes

Topical Cyclosporins 0.05% eye drops twice in one eye for 3 months

Drug: Cyclosporins

Cyclosporins eye drops to be administered in dry eyes

Other Names:

Restasis

Active Comparator: Tacrolimus 0.03% treated eyes

Topical Tacrolimus 0.03% eye drops twice in one eye for 3 months

Drug: Tacrolimus

Tacrolimus eye drops to be administered in dry eyes

Other Names:

FK506

Outcome Measures

Primary Outcome Measures

Comparison between the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops on tear film volume in dry eyes in Secondary Sjogren Syndrome patients. [3 months follow up]
Tear film volume will be evaluated using Schirmer I test in millimetres in seconds in dry eyes before and after prescribing either cyclosporine or tacrolimus eye drops in Secondary Sjogren Syndrome patients.
Evaluating the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops on ocular surface damage in dry eyes in Secondary Sjogren Syndrome patients. [3 months follow up]
Ocular surface damage will be assessed in term of calculating ocular surface staining score in dry eyes of Secondary Sjogren Syndrome patients before start and at end of treatment in cyclosporine and tacrolimus treated eyes.
Studying the effect of cyclosporine and tacrolimus eye drops on tear film stability in dry eyes in Secondary Sjogren Syndrome patients. [3 months follow up]
Tear film stability will be described in form of tear film break up time in seconds in treated dry eyes of Secondary Sjogren Syndrome patients before and after adminstration of cyclosporine and tacrolimus eye drops.

Secondary Outcome Measures

Evaluating the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops on meibomian glands secretion in dry eyes of Secondary Sjogren Syndrome patients. [3 months follow up]
Comparing between effect of topical cyclosporine 0.05% and tacrolimus 0.03 % on meibomian glands secretions quality score in dry eyes of Secondary Sjogren Syndrome patients.
Studying the effect of topical application of Tacrolimus 0.03% (FK506) eye drops versus Cyclosporine 0.05% eye drops on expressibility of meibomian glands in dry eyes of Secondary Sjogren Syndrome patients. [3 months follow up]
Evaluating the effect of topical cyclosporine 0.05% and tacrolimus 0.03 % on meibomian glands expressibility score in dry eyes of Secondary Sjogren Syndrome patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed as Secondary Sjogren syndrome according to the 2002 American European consensus group (AECG) criteria, which require the presence of well defined major connective tissue disease (such as rheumatoid arthritis and systemic lupus erythematosus.
All patients show chronic symptoms of burning, foreign body sensation, itching in both eyes, abnormal Schirmer test <5 mm wetting of the paper after 5 minutes, and abnormal tear breakup time (TBUT) < 10 seconds.
Wash out period of 30 days before start of the immunomodulatory eye drops included in the investigator's study

Exclusion Criteria:

Any inflammation or active structural changes in the iris or anterior chamber.
Patients receiving or who had received systemic cyclosporine or tacrolimus.
Patients receiving any systemic drug that can cause dry eye as some antidepressants , antihistaminic drugs , hormonal therapy…etc
Glaucoma.
Previous ocular surgery.
Use of any topical medication other than artificial tears.
Contact lens wearers.
Presence of any corneal infection.
Any corneal diseases (ulcer, opacity, scar, bullous keratopathy, symblepharon or tumors).
Deforming structural lid or conjunctival abnormality.
Pregnancy.
Prior diagnosis of any of the following conditions would exclude participation in AECG study :

Past head and neck radiation treatment Hepatitis C infection Acquired immunodeficiency disease (AIDS) Pre-existing lymphoma Sarcoidosis Graft versus host disease