Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

NCT ID: NCT01850979

Last Updated: 2013-05-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-28

Study Completion Date

2011-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sjogren Syndrome Dry Eye Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Tacrolimus

Intervention Type DRUG

tacrolimus 0,03% eyedrops (olive oil vehicle) every 12 hours for 3 months placebo : olive oil eyedrops every 12 hours for 3 months

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.

Group Type PLACEBO_COMPARATOR

Olive Oil

Intervention Type DRUG

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.

Interventions

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Tacrolimus

tacrolimus 0,03% eyedrops (olive oil vehicle) every 12 hours for 3 months placebo : olive oil eyedrops every 12 hours for 3 months

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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FK 506 placebo

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Sao Paulo General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fernando Eiji Sakassegawa Naves

physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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ruth m santo, assistent

Role: STUDY_CHAIR

University of Sao Paulo General Hospital

Locations

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University of Sao Paulo General Hospital

São Paulo, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Felberg S, Dantas PE. [Sjogren's syndrome: diagnosis and treatment]. Arq Bras Oftalmol. 2006 Nov-Dec;69(6):959-63. doi: 10.1590/s0004-27492006000600032. Portuguese.

Reference Type BACKGROUND
PMID: 17273698 (View on PubMed)

The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):75-92. doi: 10.1016/s1542-0124(12)70081-2.

Reference Type BACKGROUND
PMID: 17508116 (View on PubMed)

Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):163-78. doi: 10.1016/s1542-0124(12)70085-x.

Reference Type BACKGROUND
PMID: 17508120 (View on PubMed)

Shoji J, Sakimoto T, Muromoto K, Inada N, Sawa M, Ra C. Comparison of topical dexamethasone and topical FK506 treatment for the experimental allergic conjunctivitis model in BALB/c mice. Jpn J Ophthalmol. 2005 May-Jun;49(3):205-10. doi: 10.1007/s10384-004-0187-3.

Reference Type BACKGROUND
PMID: 15944824 (View on PubMed)

Moscovici BK, Holzchuh R, Chiacchio BB, Santo RM, Shimazaki J, Hida RY. Clinical treatment of dry eye using 0.03% tacrolimus eye drops. Cornea. 2012 Aug;31(8):945-9. doi: 10.1097/ICO.0b013e31823f8c9b.

Reference Type BACKGROUND
PMID: 22511024 (View on PubMed)

Attas-Fox L, Barkana Y, Iskhakov V, Rayvich S, Gerber Y, Morad Y, Avni I, Zadok D. Topical tacrolimus 0.03% ointment for intractable allergic conjunctivitis: an open-label pilot study. Curr Eye Res. 2008 Jul;33(7):545-9. doi: 10.1080/02713680802149115.

Reference Type BACKGROUND
PMID: 18600486 (View on PubMed)

Bertelmann E, Pleyer U. Immunomodulatory therapy in ophthalmology - is there a place for topical application? Ophthalmologica. 2004 Nov-Dec;218(6):359-67. doi: 10.1159/000080937.

Reference Type BACKGROUND
PMID: 15564752 (View on PubMed)

Fei WL, Chen JQ, Yuan J, Quan DP, Zhou SY. Preliminary study of the effect of FK506 nanospheric-suspension eye drops on rejection of penetrating keratoplasty. J Ocul Pharmacol Ther. 2008 Apr;24(2):235-44. doi: 10.1089/jop.2007.0059.

Reference Type BACKGROUND
PMID: 18321198 (View on PubMed)

Fujita E, Teramura Y, Mitsugi K, Ninomiya S, Iwatsubo T, Kawamura A, Kamimura H. Absorption, distribution, and excretion of 14C-labeled tacrolimus (FK506) after a single or repeated ocular instillation in rabbits. J Ocul Pharmacol Ther. 2008 Jun;24(3):333-43. doi: 10.1089/jop.2007.0086.

Reference Type BACKGROUND
PMID: 18476802 (View on PubMed)

Fujita E, Teramura Y, Shiraga T, Yoshioka S, Iwatsubo T, Kawamura A, Kamimura H. Pharmacokinetics and tissue distribution of tacrolimus (FK506) after a single or repeated ocular instillation in rabbits. J Ocul Pharmacol Ther. 2008 Jun;24(3):309-19. doi: 10.1089/jop.2007.0083.

Reference Type BACKGROUND
PMID: 18476801 (View on PubMed)

Pleyer U, Lutz S, Jusko WJ, Nguyen KD, Narawane M, Ruckert D, Mondino BJ, Lee VH, Nguyen K. Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye. Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2737-42.

Reference Type BACKGROUND
PMID: 7688360 (View on PubMed)

Ohashi Y, Ebihara N, Fujishima H, Fukushima A, Kumagai N, Nakagawa Y, Namba K, Okamoto S, Shoji J, Takamura E, Hayashi K. A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2010 Apr;26(2):165-74. doi: 10.1089/jop.2009.0087.

Reference Type BACKGROUND
PMID: 20307214 (View on PubMed)

Dhaliwal JS, Mason BF, Kaufman SC. Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty. Cornea. 2008 May;27(4):488-93. doi: 10.1097/ICO.0b013e3181606086.

Reference Type BACKGROUND
PMID: 18434855 (View on PubMed)

Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH; European Study Group on Classification Criteria for Sjogren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554-8. doi: 10.1136/ard.61.6.554.

Reference Type BACKGROUND
PMID: 12006334 (View on PubMed)

van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 1969 Jul;82(1):10-4. doi: 10.1001/archopht.1969.00990020012003. No abstract available.

Reference Type BACKGROUND
PMID: 4183019 (View on PubMed)

Toda I, Tsubota K. Practical double vital staining for ocular surface evaluation. Cornea. 1993 Jul;12(4):366-7. doi: 10.1097/00003226-199307000-00015. No abstract available.

Reference Type BACKGROUND
PMID: 7687944 (View on PubMed)

Moscovici BK, Holzchuh R, Sakassegawa-Naves FE, Hoshino-Ruiz DR, Albers MB, Santo RM, Hida RY. Treatment of Sjogren's syndrome dry eye using 0.03% tacrolimus eye drop: Prospective double-blind randomized study. Cont Lens Anterior Eye. 2015 Oct;38(5):373-8. doi: 10.1016/j.clae.2015.04.004. Epub 2015 May 5.

Reference Type DERIVED
PMID: 25956572 (View on PubMed)

Other Identifiers

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1307/09

Identifier Type: -

Identifier Source: org_study_id

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