Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Fernando Eiji Sakassegawa Naves, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01850979
First received: May 1, 2013
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Sjogren Syndrome
Dry Eye Syndrome
Drug: Tacrolimus
Drug: Olive Oil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops: Prospective Double-Blind Randomized Study

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • Evaluation of the quantity of lacrimal film [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Evaluation of quality of lacrimal film [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Evaluation of ocular surface [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    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


Enrollment: 24
Study Start Date: February 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: placebo

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.

  Eligibility

Ages Eligible for Study:   40 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01850979

Locations
Brazil
University of Sao Paulo General Hospital
Sao Paulo, SP, Brazil, 05403000
Sponsors and Collaborators
University of Sao Paulo General Hospital
Investigators
Study Chair: ruth m santo, assistent University of Sao Paulo General Hospital
  More Information

Publications:

Responsible Party: Fernando Eiji Sakassegawa Naves, physician, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01850979     History of Changes
Other Study ID Numbers: 1307/09
Study First Received: May 1, 2013
Last Updated: May 9, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by University of Sao Paulo General Hospital:
CYCLOSPORINE/TACROLIMUS [VA Drug Interaction]

Additional relevant MeSH terms:
Dry Eye Syndromes
Keratoconjunctivitis Sicca
Sjogren's Syndrome
Lacrimal Apparatus Diseases
Eye Diseases
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Keratitis
Corneal Diseases
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tetrahydrozoline
Ophthalmic Solutions
Tacrolimus
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents

ClinicalTrials.gov processed this record on August 01, 2014