Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease

NCT ID: NCT03399175

Last Updated: 2023-05-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-23
• Study Completion Date: 2025-02-28

Brief Summary

This prospective study will include patients with Vogt-Koyanagi-Harada disease from disease onset, treated with early systemic high-dose corticosteroid and immunosuppressive therapy. Clinical and subclinical signs of disease activity added with electroretinogram exams, through predefined intervals, will be evaluated through a minimum 12-month follow-up.

Detailed Description

Vogt-Koyanagi-Harada disease (DVKH) is an autoimmune disorder, which is mainly a T CD4+ Th1 lymphocyte mediated aggression to melanocytes, in individuals with a genetic predisposition, in particular, the presence of HLA-DRB1*0405 allele. It is an important cause of non-infectious uveitis at tertiary services in Brazil and a major cause of uveitis in general, in some regions of the world, such as in Japan and Asia. Its clinical course is classically defined in four phases: prodromal, with general symptoms possibly related to a viral trigger; uveitic, with sudden decrease in visual acuity in both eyes with a diffuse choroiditis associated or not to iridocyclitis; convalescent, wherein the depigmentation of the integument and choroid is more evident, with an apparently quiescent disease from a clinical point of view; and chronic or recurrent, in which the predominant inflammatory signs of anterior segment are clinically detected and complications are more evident, such as choroidal neovascularization, cataract and glaucoma.

Recent studies have shown subclinical inflammation of the choroid, detected by indocyanine green angiography (ICGA) and also by enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Several authors have been taking these findings into account for inflammation monitoring and treatment follow-up. However, the wider knowledge of these subclinical signs of inflammation and the understanding of the disease's course from a global perspective are still scarce. The study developed by Sakata et al. (2012-2015) established an early and aggressive treatment with pulsetherapy of methylprednisolone, followed by high doses of oral prednisone (1 mg / kg / day) with slow and gradual tapering over a 15-month period. Such study has showed that, despite an "adequate" treatment: a) 94% of patients had worsening of visual acuity or disease relapse during a 12-month follow-up; b) subclinical signs fluctuated without changing the initial treatment ; c) particular cases, in which there was an increase of treatment, showed better retinal function at final follow-up.

Thus, this study aims to continue the evaluation of subclinical signs and their clinical and functional relevance, as well as, with an early immunomodulatory treatment, to observe the clinical course of DVKH and its behavior in functional terms and development of complications. Study design: prospective and longitudinal, with a minimum 12-month follow-up, with integrated clinical, angiographic, tomographic and functional assessments. On clinical examination, anterior segment inflammatory signs will be evaluated (cells in anterior chamber), as well as posterior findings (observed in the acute phase: optic disc hyperemia, exudative retinal detachment, macular edema, vasculitis, vitreous haze); on angiographic evaluation, fluorescein angiogram (FA) and ICGA will be included; on tomographic evaluation, evaluation of retina and choroid will be included (EDI-OCT); and, on the functional tests, it will be included: the full-field electroretinography (ERGct) and multifocal electroretinography (ERGmf); as well as autofluorescence (AF) with blue light (Bl-AF) and near-infrared light (NIR-AF); automated perimetry (30-2) and contrast sensitivity test. Quality of life questionnaires and visual function evaluation will be included in pre-defined intervals.

Expected results: 1. To reaffirm the importance of an integrated analysis of the clinical and ancillary tests for better patient monitoring and to improve disease prognosis; 2. To increase the understanding of the disease natural course; 3. To increase the understanding of the disease pathogenesis; and, 4. To set parameters (outcomes) that can guide therapy.

Conditions

Vogt Koyanagi Harada Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Treatment group

Early high-dose corticosteroid and immunosuppressive therapy

Group Type: OTHER

Early high-dose corticosteroid and immunosuppressive therapy

Intervention Type: DRUG

Early high-dose corticosteroid and immunosuppressive therapy

Interventions

Early high-dose corticosteroid and immunosuppressive therapy

Early high-dose corticosteroid and immunosuppressive therapy

Intervention Type: DRUG

Other Intervention Names

Treatment group

Eligibility Criteria

Inclusion Criteria

• acute Vogt-Koyanagi-Harada disease

Exclusion Criteria

• non collaborative patient
• minimum one-year follow-up

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Joyce Hisae Yamamoto

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joyce H Yamamoto, MD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo School of Medicine Ophthalmology

Locations

Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Joyce H Yamamoto, MD

Role: CONTACT

joycehy@uol.com.br

55-11-99266-6474

Facility Contacts

Joyce Yamamoto, MD

Role: primary

joycehy@uol.com.br

11992666474

Marcelo M Lavezzo, MD

Role: backup

mmlavezzo@gmail.com

References

Lavezzo MM, Sakata VM, Morita C, Rodriguez EE, Abdallah SF, da Silva FT, Hirata CE, Yamamoto JH. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes. Orphanet J Rare Dis. 2016 Mar 24;11:29. doi: 10.1186/s13023-016-0412-4.

Reference Type: RESULT

PMID: 27008848 (View on PubMed)

Sakata VM, da Silva FT, Hirata CE, de Carvalho JF, Yamamoto JH. Diagnosis and classification of Vogt-Koyanagi-Harada disease. Autoimmun Rev. 2014 Apr-May;13(4-5):550-5. doi: 10.1016/j.autrev.2014.01.023. Epub 2014 Jan 15.

Reference Type: RESULT

PMID: 24440284 (View on PubMed)

Damico FM, Bezerra FT, Silva GC, Gasparin F, Yamamoto JH. New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009 May-Jun;72(3):413-20. doi: 10.1590/s0004-27492009000300028.

Reference Type: RESULT

PMID: 19668980 (View on PubMed)

da Silva FT, Damico FM, Marin ML, Goldberg AC, Hirata CE, Takiuti PH, Olivalves E, Yamamoto JH. Revised diagnostic criteria for vogt-koyanagi-harada disease: considerations on the different disease categories. Am J Ophthalmol. 2009 Feb;147(2):339-345.e5. doi: 10.1016/j.ajo.2008.08.034. Epub 2008 Nov 7.

Reference Type: RESULT

PMID: 18992868 (View on PubMed)

da Silva FT, Hirata CE, Olivalves E, Oyamada MK, Yamamoto JH. Fundus-based and electroretinographic strategies for stratification of late-stage Vogt-Koyanagi-Harada disease patients. Am J Ophthalmol. 2009 Dec;148(6):939-45.e3. doi: 10.1016/j.ajo.2009.06.029. Epub 2009 Sep 24.

Reference Type: RESULT

PMID: 19781687 (View on PubMed)

da Silva FT, Hirata CE, Sakata VM, Olivalves E, Preti R, Pimentel SL, Gomes A, Takahashi WY, Costa RA, Yamamoto JH. Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study. BMC Ophthalmol. 2012 Aug 13;12:40. doi: 10.1186/1471-2415-12-40.

Reference Type: RESULT

PMID: 22889440 (View on PubMed)

da Silva FT, Sakata VM, Nakashima A, Hirata CE, Olivalves E, Takahashi WY, Costa RA, Yamamoto JH. Enhanced depth imaging optical coherence tomography in long-standing Vogt-Koyanagi-Harada disease. Br J Ophthalmol. 2013 Jan;97(1):70-4. doi: 10.1136/bjophthalmol-2012-302089. Epub 2012 Oct 25.

Reference Type: RESULT

PMID: 23099292 (View on PubMed)

Sakata VM, da Silva FT, Hirata CE, Takahashi WY, Costa RA, Yamamoto JH. Choroidal bulging in patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage. J Ophthalmic Inflamm Infect. 2014 Feb 18;4(1):6. doi: 10.1186/1869-5760-4-6.

Reference Type: RESULT

PMID: 24548697 (View on PubMed)

Sakata VM, da Silva FT, Hirata CE, Marin ML, Rodrigues H, Kalil J, Costa RA, Yamamoto JH. High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids. Graefes Arch Clin Exp Ophthalmol. 2015 May;253(5):785-90. doi: 10.1007/s00417-014-2904-z. Epub 2015 Jan 16.

Reference Type: RESULT

PMID: 25592477 (View on PubMed)

Morita C, Sakata VM, Rodriguez EE, Abdallah SF, Lavezzo MM, da Silva FT, Machado CG, Oyamada MK, Hirata CE, Yamamoto JH. Fundus autofluorescence as a marker of disease severity in Vogt-Koyanagi-Harada disease. Acta Ophthalmol. 2016 Dec;94(8):e820-e821. doi: 10.1111/aos.13147. Epub 2016 Jul 2. No abstract available.

Reference Type: RESULT

PMID: 27368955 (View on PubMed)

Herbort CP Jr, Abu El Asrar AM, Yamamoto JH, Pavesio CE, Gupta V, Khairallah M, Tugal-Tutkun I, Soheilian M, Takeuchi M, Papadia M. Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality. Int Ophthalmol. 2017 Dec;37(6):1383-1395. doi: 10.1007/s10792-016-0395-0. Epub 2016 Nov 14.

Reference Type: RESULT

PMID: 27844182 (View on PubMed)

Other Identifiers

VKH Brazilian Study Group

Identifier Type: -

Identifier Source: org_study_id