Hydroxychloroquine Treatment of Dry Eyes in Patients With Primary Sjögren's Syndrome

Study Overview
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Brief Summary
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Primary Sjögren syndrome is one of the most prevalent autoimmune diseases that present with dry eye and dry mouth. But there is no proven effective treatment for Sjögren syndrome patient. The relation between toll-like receptor (TLR) and the pathogenesis of Sjögren syndrome has been reported. Hydroxychloroquine is TLR7 and TLR9 antagonist. A few studies have been reported the effectiveness of Hydroxychloroquine for Sjögren syndrome but no randomized controlled study has been done. So the investigators evaluate the effectiveness and safeness of Hydroxychloroquine for primary Sjögren syndrome by randomized controlled study (Hydroxychloroquine 300 mg once daily p.o. group (N = 30) versus placebo group (N = 30).

Official Title
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Phase 3 Study of Hydroxychloroquine Treatment of Dry Eyes in Patients With Primary Sjögren's Syndrome

Conditions
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Autoimmune Diseases, Sjogren's Syndrome, Dry Eye

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who is diagnosed with primary Sjögren syndrome according to American/European consensus group (AECG) criteria Patient with the ability to give informed, dated and signed consent before the beginning of any proceedings related to the trial Exclusion Criteria: Previous treated by Hydroxychloroquine but enough washout time after discontinuance of treatment, patient can be enrolled. (2 wks) Known cardiac disease, Respiratory disease, Renal disease, Gastrointestinal disease (except GERD) Diabetes mellitus Psoriasis Known drug allergy or hypersensitivity Previous or ongoing treatment by any drugs (include topical drug) which have effect on lacrimal system. But enough washout time after discontinuance of treatment, patient can be enrolled. (cf. SSRI, Anti-histamine, Pilocarpine, etc.) Angle closer glaucoma Patient who underwent previous intraocular surgery Macular disease Previous or ongoing treatment by drug which could have effect on macula Pregnancy Planning to get pregnant

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br>Hydroxychloroquine 300 mg once daily p.o. | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 300 mg once daily p.o. for 12 weeks and go off medication for 4 weeks (total 16 weeks)<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 2cp/day for 12 weeks and go off medication for 4 weeks (total 16 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokine level | IL-6, IL-17, IL-1b, TNF-alpha, INF-alpha, BAFF, etc. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal exam | Macular exam for monitoring Hydroxychloroquine macular toxicity | 16 weeks | 
| Indicator of inflammation | Serum ESR | 16 weeks | 
| Tear production | Schirmer's test | 16 weeks | 
| Subjective clinical eye complaints | Ocular Surface Disease Index (OSDI) | 16 weeks | 
| Tear cytokine level | IL-6, IL-17, IL-1b, TNF-alpha, INF-alpha, BAFF, etc. | 16 weeks | 
| Visual acuity | Best corrected visual acuity (Snellen) | 16 weeks | 
| Color test | HRR color vision test for monitoring hydroxychloroquine retinal toxicity | 16 weeks | 
| Tear breakup time | BUT (sec) | 16 weeks | 
| Corneal punctate fluorescein staining score | Corneal staining score (National Eye Institute Scale) | 16 weeks | 
| Changes in serum T-cell property | Serum T-cell property (FACS) | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Diseases, Sjogren's Syndrome, Hydroxychloroquine