Effect of B-cell Depletion in Patients With Primary Sjögren's Syndrome

This study has been completed.
Sponsor:
Collaborator:
Rigshospitalet, Denmark
Information provided by:
University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00426543
First received: January 23, 2007
Last updated: January 13, 2011
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Primary Sjogren's Syndrome
Xerostomia
Keratoconjunctivitis Sicca
Fatigue
Drug: MabThera (rituximab)
Drug: Rituximab, Mabthera
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase 1 Study of B-cell Depletion With Rituximab on Oral, Ocular and General Disease Manifestations in Patients With Primary Sjögren's Syndrome

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue. [ Time Frame: Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study the effect of Rituximab: on the structural changes (focal lymphocytic infiltrates) in the labial salivary gland tissue, including changes in the T- and B-cell ratio in the infiltrates as well as in the expression of M3-receptors [ Time Frame: Baseline and 6 months after treatment ] [ Designated as safety issue: No ]
  • On the salivary gland function, incl. the production and composition of whole saliva and parotid saliva, the cellular signalling mechanisms and also the distribution of M3-receptors (M3R), the expression of aquaporins, [ Time Frame: Baseline, 1 month, 3 months and 6 months after treatment ] [ Designated as safety issue: No ]
  • On the circulating serum autoantibodies (anti-SSA/-SSB, rheumatoid factors) and on antibodies against the M3R and α-fodrin and on the IgG level. [ Time Frame: Baseline, 1 month, 3 months and 6 months after treatment ] [ Designated as safety issue: No ]
  • On the phenotype of circulating T- and B-cells as well as cytokines and immunoregulators, especially BLyS/BAFF. [ Time Frame: Baseline, 1 month, 3 months and 6 months after treatment ] [ Designated as safety issue: No ]
  • On the function of the tear glandula, including the quantity and quality of tear as well as the extent of corneal changes. [ Time Frame: Baseline, 1 month, 3 months and 6 months after treatment ] [ Designated as safety issue: No ]
  • To evaluate the side-effects in relation to the use of Rituximab-/placebo treatment. [ Time Frame: After first and second treatment and after 1 month ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: January 2007
Study Completion Date: August 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: MabThera (rituximab)
    1000 mg infusion twice with 14 days interval
    Other Name: Mabthera
    Drug: Rituximab, Mabthera
    1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female patients fulfilling the current American-European consensus classification criteria.
  • Fertile-age female patients must use safe anticonceptional methods such as pills, mini-pills, or intrauterine spiral.
  • The fertile-age females included in the study must not get pregnant in at least 12 months after the last treatment with Rituximab.

Exclusion Criteria:

  • Pregnancy and lactation.
  • Fertile-age females who do not use safe anticonceptional methods.
  • Patients in systemic treatment with cytostatics.
  • Patients who previously have been treated with Rituximab.
  • Patient with an active infection that requires antibiotic treatment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00426543

Locations
Denmark
Institute of Odontology, Faculty of Health Sciences, University of Copenhagen
Copenhagen, Denmark, 2200
Sponsors and Collaborators
University of Copenhagen
Rigshospitalet, Denmark
Investigators
Principal Investigator: Anne Marie Lynge Pedersen, PhD, DDS Institute of Odontology, Faculty of Health Sciences, University of Copenhagen
  More Information

Publications:
Responsible Party: Anne Marie Lynge Pedersen, University of Copenhagen and Rigshospitalet
ClinicalTrials.gov Identifier: NCT00426543     History of Changes
Other Study ID Numbers: KF 02 282294, EudractCT-no. 2005-004740-31
Study First Received: January 23, 2007
Last Updated: January 13, 2011
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Keywords provided by University of Copenhagen:
Clinical trial
Intervention study
Double-blind randomised controlled study

Additional relevant MeSH terms:
Keratoconjunctivitis Sicca
Dry Eye Syndromes
Fatigue
Keratoconjunctivitis
Xerostomia
Sjogren's Syndrome
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Keratitis
Corneal Diseases
Lacrimal Apparatus Diseases
Signs and Symptoms
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014