Effect of B-cell Depletion in Patients With Primary Sjögren's Syndrome
Condition: Primary Sjögren's Syndrome; Xerostomia; Hyposalivation; Keratoconjunctivitis Sicca; Fatigue
MeSH terms: Sjogren's Syndrome; Xerostomia; Keratoconjunctivitis; Keratoconjunctivitis Sicca; Dry Eye Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary purpose of the study is to determine whether B-cell depletion with Rituximab has
      an effect on the oral, ocular and general disease manifestations in patients with primary
      Sjögren´s syndrome, that is, an effect on the symptoms of oral and ocular dryness,
      improvement of the glandular function and a beneficial effect on the general symptoms such as
      fatigue. The secondary purpose of the study is the investigate the underlying autoimmune and
      pathophysiological mechanisms in Sjögren´s syndrome.
    

Detailed description: 
      The trial is designed as a double-blind parallel comparison between 2 infusions of 1 g
      Rituximab and solvent (saline) given two weeks apart, in 22 patients with the diagnosis of
      primary Sjögren's syndrome as based on the current American-European consensus classification
      criteria. The patients will be followed at the Department of Oral Medicine, Clinical Oral
      Physiology, Oral Pathology & Anatomy, University of Copenhagen, the Department of
      Rheumatology, Rigshospitalet and at the Department of Ophthalmology, Rigshospitalet.

      The primary endpoints are clinical and a response has been delineated as at least 50%
      improvement in score. With the provision that this occurs for any item in at least 60% of the
      treated patients as compared to 1% in the control patients, a power of over 80% at doubled
      sided significance level of 5% is found with 20 patients.The patients will be followed within
      this study for 6 months after Rituximab.

      The study will allow the first real dynamic appraisal of the immunologic pathophysiology in
      Sjögren's syndrome. Hence attempts will be made to determine at the best possible level if
      and how Rituximab influences and possibly resets the autoimmunity both at the whole body and
      particularly at the local level in the salivary glands. Also the basal transport mechanism in
      salivary secretion which must necessarily be perturbed in Sjögren's syndrome will be
      scrutinized employing the best available of techniques. Every possible effort to envisage a
      priory, and then monitor, the decisive mechanisms has been made.

      In particular this includes repetitive biopsies from the parotid glands, which will allow
      combining functional and structural data to reduce as much as possible random variability of
      crucial quantities. Also this will allow for the first time to assess the relative and
      combined utility of obtaining biopsies from both the parotid and labial salivary glands.

      Roche A/S provide investigational medicine, but the study was initiated and is entirely
      controlled by the investigators.
    

Intervention name(s): MabThera (rituximab); Rituximab, Mabthera
Intervention type(s): Drug; Drug
Intervention description(s): 1000 mg infusion twice with 14 days interval; 1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval
Other intervention name(s): Mabthera
Intervention MeSH terms: Rituximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Clinical trial; Intervention study; Double-blind randomised controlled study