Hydroxychloroquine Versus Placebo in Primary Sjögren's Syndrome

Study Overview
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Brief Summary
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Primary Sjögren's syndrome (SJp) affects 0.1% of the population. This systemic autoimmune disease systemic is characterized by disabling dryness, fatigue and pain, and systemic complications in 30% of patients. No treatment has proven effective in this disease. In open studies, some efficacy was observed with hydroxychloroquine but no RCT versus placebo has ever been done. Thus, the primary purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine (400mg/ day) on dryness, pain, and fatigue, assessed by the patient using visual analogical scales.

Detailed Description
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Primary Sjögren's syndrome (SJp) affects 0.1% of the population. This systemic autoimmune disease systemic is characterized by disabling dryness, fatigue and pain, and systemic complications in 30% of patients. No treatment has proven effective in this disease. In open studies, some efficacy was observed with hydroxychloroquine but no RCT versus placebo has ever been done. Thus, the primary purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine (400mg/ day) on dryness, pain, and fatigue, assessed by the patient using visual analogical scales (VAS). Response is defined by the improvement of 30% or more of at least 2 out of 3 of the following VAS : most disabling dryness, fatigue, and pain.

Official Title
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Randomized, Double-blind, Placebo-controlled Trial of Hydroxychloroquine in Primary Sjögren's Syndrome

Conditions
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Primary Sjögren's Syndrome

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients suffering from primary Sjögren's syndrome according to the European-American consensus group criteria Male and female aged of 18 or more Conducting a clinical examination beforehand. Having undergone less than 6 months before an ophthalmological examination, which did not counter-indicated hydroxychloroquine. Patient without heart conduction disturbance (PR>=0.2 sec and QRS>=0.08 sec). Patient with the ability to give informed, dated and signed consent before the beginning of any proceedings related to the trial Patients treated with corticosteroids and / or NSAIDs, and / or cyclosporine, and / or pilocarpine must have received stable doses of these treatments during the month preceding inclusion. Exclusion criteria: SJ associated with other autoimmune diseases Retinopathy /severe cataract/ monophthalmos Previous or ongoing treatment by hydroxychloroquine Treatment by another immunosuppressant not interrupted at least 4 weeks prior to inclusion, or 6 months prior to inclusion for cyclophosphamide or rituximab lymphoma or other severe SJp complications: vasculitis responsible for a documented renal, neurological, digestive or heart involvement, glomerular disease associated with hematuria and / or proteinuria > 0.5 g / d), CNS involvement, peripheral neurological involvement with motor deficiency scored at 3 or less on a scale of 5 , interstitial pneumonitis, recent symptomatic cryoglobulinemia with neurological, renal, or other systemic involvement, myositis with motor deficiency (isolated purpura is not an exclusion criteria) Chronic Alcoholism Hepato-cellular insufficiency Creatinine clearance <60 ml / min Risk of lost follow-up People younger than 18, major trusteeship and guardianship, or deprived of liberty Pregnancy /Breastfeeding Hypersensitivity to chloroquine or to hydroxychloroquine or any of the other constituents of Plaquenil Psoriasis or intermittent porphyria. G6PD deficiency, congenital galactosemia, malabsorption syndrome, glucose and galactose, or lactase deficiency. Non-membership in a social security system.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: 1<br>Active treatment : Hydroxychloroquine | Drug: Hydroxychloroquine<br>* Hydroxychloroquine : 200mg / day since 24 weeks<br>* Other names: Plaquenil;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo : 2cp/ day since 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an improvement of 30% or more of at least 2 out of the 3 following VAS: 1. the most disabling dryness 2. pain 3. fatigue |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCHIRMER's test, van BIJSTERVELD score, salivary flow, disease systemic features, quality of life, interferon-inducible genes expression Association between clinical response and hydroxychloroquine blood level, interferon-inducible genes expression |  | 6 mois | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auto-immune diseases, hydroxychloroquine, primary Sjögren's syndrome, inflammatory arthritides, inflammatory rheumatic diseases, dryness, joint diseases