Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

NCT01850979 | Completed Phase 4

• 1 other identifier: 1307/09
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sjogren Syndrome; Dry Eye Syndrome

Keywords

CYCLOSPORINE/TACROLIMUS [VA Drug Interaction]

Outcome Measures

Primary Outcomes (1)

• Evaluation of the quantity of lacrimal film

  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 Outcomes (1)

• Evaluation of quality of lacrimal film

  90 days

Other Outcomes (1)

• Evaluation of ocular surface

  90 days

Study Arms (2)

tacrolimus

ACTIVE COMPARATOR

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

Olive Oil

PLACEBO COMPARATOR

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

Interventions

Tacrolimus DRUG

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

Also known as: FK 506

tacrolimus

Olive Oil 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.

Also known as: placebo

Olive Oil

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

University of Sao Paulo General Hospital

São Paulo, São Paulo, 05403000, Brazil

Location

Related Publications (17)

• 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.

  PMID: 17273698 BACKGROUND

• 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.

  PMID: 17508116 BACKGROUND

• 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.

  PMID: 17508120 BACKGROUND

• 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.

  PMID: 15944824 BACKGROUND

• 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.

  PMID: 22511024 BACKGROUND

• 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.

  PMID: 18600486 BACKGROUND

• 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.

  PMID: 15564752 BACKGROUND

• 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.

  PMID: 18321198 BACKGROUND

• 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.

  PMID: 18476802 BACKGROUND

• 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.

  PMID: 18476801 BACKGROUND

• 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.

  PMID: 7688360 BACKGROUND

• 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.

  PMID: 20307214 BACKGROUND

• 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.

  PMID: 18434855 BACKGROUND

• 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.

  PMID: 12006334 BACKGROUND

• 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.

  PMID: 4183019 BACKGROUND

• 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.

  PMID: 7687944 BACKGROUND

• 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.

  PMID: 25956572 DERIVED

MeSH Terms

Conditions

Sjogren's Syndrome; Dry Eye Syndromes

Interventions

Tacrolimus; Olive Oil

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• ruth m santo, assistent

  University of Sao Paulo General Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: physician

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 10, 2013
• Study Start: February 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: May 10, 2013

Record last verified: 2013-05

Locations

BR (1)