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

Vogt Koyanagi Harada Disease Clinical Trial

Official title:

Influência de imunomodulação Precoce Influence of Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease: a Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03399175
• Other study ID #: VKH Brazilian Study Group
• Status: Recruiting
• Phase: N/A
• Start date: March 23, 2015
• Est. completion date: February 2025

Study information

• Verified date: May 2023
• Source: University of Sao Paulo
• Contact: Joyce H Yamamoto, MD
• Phone: 55-11-99266-6474
• Email: joycehy[@]uol.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 2025
• Est. primary completion date: May 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 70 Years

Eligibility

Inclusion criteria:

• acute Vogt-Koyanagi-Harada disease

Exclusion criteria:

• non collaborative patient

• minimum one-year follow-up

Related Conditions & MeSH terms

• Uveomeningoencephalitic Syndrome
• Vogt Koyanagi Harada Disease

Intervention

Drug:
• Early high-dose corticosteroid and immunosuppressive therapy
Early high-dose corticosteroid and immunosuppressive therapy

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo	São Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (11)

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. — View Citation

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.2009.06.0 — View Citation

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 — View Citation

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/bjophth — View Citation

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. — View Citation

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. 20 — View Citation

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/s130 — View Citation

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. do — View Citation

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. — View Citation

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 M — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	scotopic electroretinogram results	scotopic results variation between 12 months and 6 months	6 month; 12 month
Secondary	presence of optic disc hyperfluorescence detected on fluorescein angiography	presence of optic disc hyperfluorescence and variation in intensity in consecutive examinations	between 6 and 12 months from disease onset.
Secondary	presence of perivascular leakage on fluorescein angiography	presence of perivascular leakage and variation in extension and intensity in consecutive examinations	between 6 and 12 months from disease onset.
Secondary	presence of dark dots on indocyanine green angiography	dark dots score and its fluctuation	between 6 and 12 months from disease onset.
Secondary	subfoveal choroidal thickness on enhanced depth imaging optical coherence tomography	subfoveal choroidal thickness and its variation	between 6 and 12 months from disease onset.
Secondary	presence of cells in anterior chamber graduated according to SUN criteria	presence of cells in anterior chamber and its variation	between 6 and 12 months from disease onset.
Secondary	presence of choroidal neovascular membrane on OCT and/or FA	choroidal neovascular membrane	between 6 and 12 months from disease onset.
Secondary	presence of macular edema on OCT and/or FA	macular edema detected clinically, angiographically and/or by optical coherence tomography	between 6 and 12 months from disease onset.