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

NCT00426543 | Completed Phase 2 DMC

• 2 other identifiers: KF 02 282294EudractCT-no. 2005-004740-31
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Sjögren's Syndrome; Xerostomia; Hyposalivation; Keratoconjunctivitis Sicca; Fatigue

Keywords

Clinical trial; Intervention study; Double-blind randomised controlled study

Outcome Measures

Primary Outcomes (1)

• To investigate the effect of Rituximab on subjective disease symptoms including oral dryness, ocular dryness, myoartralgia and fatigue.

  Baseline, Day 22 after second treatment, 1 month, 3 months and 6 months after treatment.

Secondary Outcomes (6)

• 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

  Baseline and 6 months after treatment

• 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,

  Baseline, 1 month, 3 months and 6 months after treatment

• On the circulating serum autoantibodies (anti-SSA/-SSB, rheumatoid factors) and on antibodies against the M3R and α-fodrin and on the IgG level.

  Baseline, 1 month, 3 months and 6 months after treatment

• On the phenotype of circulating T- and B-cells as well as cytokines and immunoregulators, especially BLyS/BAFF.

  Baseline, 1 month, 3 months and 6 months after treatment

• On the function of the tear glandula, including the quantity and quality of tear as well as the extent of corneal changes.

  Baseline, 1 month, 3 months and 6 months after treatment

Interventions

MabThera (rituximab) DRUG

1000 mg infusion twice with 14 days interval

Also known as: Mabthera

Rituximab, Mabthera DRUG

1000 mg Rituximab infusion in 500 ml isotonic sodiumchloride twice with 14 days interval

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Copenhagen: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

Copenhagen, 2200, Denmark

Location

Related Publications (1)

• Ring T, Kallenbach M, Praetorius J, Nielsen S, Melgaard B. Successful treatment of a patient with primary Sjogren's syndrome with Rituximab. Clin Rheumatol. 2006 Nov;25(6):891-4. doi: 10.1007/s10067-005-0086-0. Epub 2005 Nov 8.

  PMID: 16283417 BACKGROUND

MeSH Terms

Conditions

Xerostomia; Keratoconjunctivitis Sicca; Fatigue

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Anne Marie Lynge Pedersen, PhD, DDS

  Institute of Odontology, Faculty of Health Sciences, University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, PhD, DDS

Study Record Dates

• First Submitted: January 23, 2007
• First Posted: January 24, 2007
• Study Start: January 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 14, 2017

Record last verified: 2017-03

Locations

DK (1)