Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

May 9, 2013 updated by: Fernando Eiji Sakassegawa Naves, University of Sao Paulo General Hospital

Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops: Prospective Double-Blind Randomized Study

Aqueous deficiency dry eye is mainly caused by Sjogren syndrome (SS), an autoimmune, chronic, inflammatory and systemic disease which affects most commonly the lacrimal and salivary glands.The ocular treatment is focused in increasing lubrification and decreasing inflammation with topical autologous serum, topical immunosuppressive agents and corticotherapy. Use of topical immunosuppressants has increased in recent years because the topical corticotherapy leads to ocular complications. The most used immunosuppressant is cyclosporine. Tacrolimus , another immunosuppressant, has been used in treatment of immune and inflammatory ocular diseases.This study describes a prospective controlled double-blinded randomized study of the clinical outcome of SS dry eyes patients treated with 0.03% tacrolimus eye drops. As secondary purposes, outcome of dry eye symptoms and any ocular symptoms of the eye drops were also questioned to the patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aqueous deficiency dry eye is mainly caused by Sjogren syndrome (SS), an autoimmune, chronic, inflammatory and systemic disease which affects most commonly the lacrimal and salivary glands. The hyperreactivity of B lymphocytes causes lymphoplasmacytic infiltration, which induces production of antibodies against antigens of the acinar epithelium and ducts of the lacrimal exocrine gland . The ocular treatment is focused in increasing lubrification and decreasing inflammation with topical autologous serum, topical immunosuppressive agents and corticotherapy. Use of topical immunosuppressants has increased in recent years because the topical corticotherapy leads to ocular complications.

Among topical immunosuppressants the most used ones are tacrolimus, also known as FK506 and cyclosporine A (CsA). Their mechanism of action is similar, but FK 506 is described to be 10 to 100 times more potent than CsA. Tacrolimus is a macrolide with immunomodulatory action and becomes biologically active only when it binds to immunophilin and acts by inhibiting calcineurin, limiting transduction of the signal that carries information from the cell membrane to the nucleus, with the aim of stimulating interleukin (IL) - 2 synthesis, and inhibiting T and B lymphocyte activation . Generally, tacrolimus suppresses the immune response by inhibiting the release of other inflammatory cytokines (eg, IL-3, IL-4, IL-5, IL-8, interferon- ϒ, and tumor necrosis factor - α) .

The systemic and topical use of tacrolimus is already well established in ophthalmologic treatments of immune-mediated diseases , uveitis, graft-versus-host disease , corneal transplants and ocular pemphigoid . In veterinary medicine, topical tacrolimus aqueous suspension is well established to treat dry eye in dogs . In humans, tacrolimus eye drops were reported to be effective in treating severe allergic conjunctivitis . In a previous report, our group has showed the clinical outcomes of a case series of eight patients with dry eye using 0.03% tacrolimus eye drops 5 based on evidence in treating animals with KCS.

This study describes a prospective controlled double-blinded randomized study of the clinical outcome of SS dry eyes patients treated with 0.03% tacrolimus eye drops. As secondary purposes, outcome of dry eye symptoms and any ocular symptoms of the eye drops were also questioned to the patients.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 05403000
        • University of Sao Paulo General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • SS was diagnosed according to the SS European Criteria
  • chronic symptoms of burning, foreign body sensation, itching in both eyes
  • daily need of artificial tears
  • abnormal Schirmer (ST) I test < 5mm or rose Bengal staining (RBS) ≥ 4, or break up time (BUT) < 5 seconds.

Exclusion Criteria:

  • any structural abnormalities (lid scarring, entropion, trichiasis, etc.)
  • any inflammation or active structural change in the iris or anterior chamber
  • glaucoma
  • previous eye surgery or punctual occlusion
  • use of any other topical medication other than artificial tears
  • any systemic or topical antibacterial or antiinflammatory drug treatment 90 days before study entry
  • contact lens wearer
  • the presence of any corneal infection
  • any corneal diseases (marginal ulcer, opacity, scar, bullous keratopathy, conjunctivochalasis, symblepharon or tumor)
  • pregnancy
  • change in the immunosuppressive systemic therapy 90 days before study entry

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: tacrolimus
tacrolimus 0,03% eye drops (olive oil as vehicle) every 12/12 hours for 3 months placebo as olive oil eye drops every 12/12h hours for 3 months
Drug: Tacrolimus
tacrolimus 0,03% eyedrops (olive oil vehicle) every 12 hours for 3 months placebo : olive oil eyedrops every 12 hours for 3 months
Other Names:
  • FK 506
Placebo Comparator: Olive Oil
All patients in this groups receive eye drops containing olive oil (vehicle of tacrolimus eye drops) twice a day (every 12 hours) for 90 days.
Drug: Olive Oil
All patients in this groups receive eye drops containing olive oil (vehicle of tacrolimus eye drops) twice a day (every 12 hours) for 90 days.
Other Names:
  • placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the quantity of lacrimal film
Time Frame: 90 days
Schirmer I test was performed using a Whatman 41 paper strip placed in the lateral lower conjunctival sac, and the measurement was recorded after 5 minutes (at least 30 minutes after BUT and staining scoring).The exam was made in the same room with control of humidity and temperature by the same examinator
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of quality of lacrimal film
Time Frame: 90 days
The BUT(break up time) was measured 3 times and averaged, using a chronometer in the same room with control of temperature and humidity by the same examinator.
90 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of ocular surface
Time Frame: 90 days
The rose bengal and fluorescein scores were performed by instilling 3 µL of a preservative-free combination of 1% rose Bengal and 1% fluorescein into the conjunctival sac according to the double vital staining method. The BUT was measured 3 times and averaged. The ocular surface staining score was rated from 0-3 (0= no staining, 1 = mild staining, 2 = moderated staining and 3 = extensive staining) . The exam was made in the same room with control of humidity and temperature by the same examinator
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Investigators

  • Study Chair: ruth m santo, assistent, University of Sao Paulo General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

May 1, 2013

First Submitted That Met QC Criteria

May 9, 2013

First Posted (Estimate)

May 10, 2013

Study Record Updates

Last Update Posted (Estimate)

May 10, 2013

Last Update Submitted That Met QC Criteria

May 9, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1307/09

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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