Clinical trial NCT00632866: Hydroxychloroquine Versus Placebo in Primary Sjögren's Syndrome
Official title: Randomized, Double-blind, Placebo-controlled Trial of Hydroxychloroquine in Primary Sjögren's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Sjögren's Syndrome
Keywords: auto-immune diseases
hydroxychloroquine
primary Sjögren's syndrome
inflammatory arthritides
inflammatory rheumatic diseases
dryness
joint diseases
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2008-03-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: 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
timeFrame: 6 mois
Other outcomes:
Locations:
city: Le Kremlin Bicetre
country: France
facility: Hopital Bicëtre
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Xavier Mariette, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gottenberg JE, Ravaud P, Puechal X, Le Guern V, Sibilia J, Goeb V, Larroche C, Dubost JJ, Rist S, Saraux A, Devauchelle-Pensec V, Morel J, Hayem G, Hatron P, Perdriger A, Sene D, Zarnitsky C, Batouche D, Furlan V, Benessiano J, Perrodeau E, Seror R, Mariette X. Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren syndrome: the JOQUER randomized clinical trial. JAMA. 2014 Jul 16;312(3):249-58. doi: 10.1001/jama.2014.7682.