Official Title: “Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxychloroquine in Primary Sjögren's Syndrome”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2010

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.

Intervention(s) in this Clinical Trial

• Drug: Hydroxychloroquine
  • Hydroxychloroquine : 200mg / day since 24 weeks
• Drug: Placebo
  • Placebo : 2cp/ day since 24 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Active treatment : Hydroxychloroquine
• Placebo Comparator: 2
  • Placebo

Primary Measures

• 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
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• 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
  • Time Frame: 6 mois
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

Xavier Mariette, MD, PhD Principal Investigator Assistance Publique - Hôpitaux de Paris  

Overall Contact: Jacques-Eric Gottenberg, MD, PhD +33 6 74 00 88 10 jegotten@club-internet.fr

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00632866

Study ID Number: P070125

ClinicalTrials.gov Identifier: NCT00632866

Health Authority: France: Ministry of Health