Mycophenolate Sodium Treatment in Patients With Primary Sjogren's Syndrome

Mycophenolate Sodium Treatment in Patients With Primary Sjogren's Syndrome - An Open Label Pilot Trial

Primary Sjogren's syndrome (pSS) is an autoimmune disorder characterized by keratoconjunctivitis sicca and xerostomia. In addition, various extraglandular manifestations may develop. Several immunomodulating agents have been attempted in the treatment of pSS without achieving satisfactory results. Currently, there is no approved systemic treatment for pSS.

Mycophenolic acid (MPA) is a selective inhibitor of inosine-monophosphate-dehydrogenase which leads to inhibition of the de novo pathway of nucleotide synthesis. The antiproliferative effect of MPA mainly affects activated T- and B-lymphocytes because the proliferation of these cells is critically dependent on the de novo purine synthesis compared to other eukaryotic cells. Since these lymphocytes have been suggested to play a pivotal role in the inflammation and immunopathogenesis of pSS, mycophenolate-sodium might be a promising agent in the treatment of pSS.

We perform a single-centre, open-label pilot trial with Mycophenolate sodium in pSS.

Study Overview

• Status: Completed
• Conditions: Primary Sjogren's Syndrome
• Intervention / Treatment: Drug: Mycophenolate sodium

Detailed Description

Mycophenolic acid containing compounds such as mycophenolate mofetil and enteric coated mycophenolate sodium are immunosuppressive drugs approved for the prevention of transplant rejection. Mycophenolate mofetil (MMF) is an effective treatment in systemic lupus erythematosus and other autoimmune diseases.

MMF has been used as maintenance therapy after treatment with rituximab (anti-CD20 antibody) in a pSS patient. We have reported a case of successful treatment with MMF in pSS with vasculitis.

The recent observations and the immunosuppressive effect of MPA in other autoimmune diseases led us to evaluate the efficacy and safety of MPA treatment in patients with pSS refractory to other immunosuppressive agents.

The observation period will be 6 months. At baseline, after 3, and after 6 months we examine the clinical status including glandular function tests as well as different laboratory parameters associated with pSS. In addition subjective parameters will be determined on the basis of different questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Muenster, NRW, Germany, 48129
      • University Hospital Muenster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of primary Sjogren' Syndrome based on the American-European Consensus criteria
• Erythrocyte sedimentation rate >25mm/h and hypergammaglobulinemia (>1500 mg/dl)
• Presence of anti-SS-A and /or SS-B antibodies and / or rheumatoid factor
• Requirement of artificial teardrops due to symptomatic sicca syndrome
• Inadequate response or intolerance of prior treatment with hydroxychloroquine and / or azathioprine
• Adequate contraception for females of childbearing potential

Exclusion Criteria:

• Age below 18 or above 75 years
• Secondary Sjogren's syndrome
• History of cancer, severe infections or other uncontrolled diseases
• Treatment with concomitant disease modifying anti-rheumatic drugs within the least 8 weeks before baseline evaluation
• Prednisolone dose of > 5mg/d or changes of prednisolone dose within the least 4 weeks before baseline
• Use of secretagogues (e.g. pilocarpine, cevimeline) or medications that potentially diminish exocrine gland function (e.g. tricyclic antidepressants, anti-cholinergic drugs)
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of mycophenolate sodium for sicca syndrome and changes in laboratory values associated with the disease	Basline, week 12 and week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of mycophenolate sodium in patients with primary Sjogren's syndrome: Clinical examination, full blood count, renal function tests, liver function tests	basline, after week 4, 12, and week 24

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: Novartis
• Investigators: Principal Investigator: Markus Gaubitz, MD, University Hospital Muenster

Publications and helpful links

General Publications

• Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH; European Study Group on Classification Criteria for Sjogren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554-8. doi: 10.1136/ard.61.6.554.
• Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjogren's syndrome. Nat Clin Pract Rheumatol. 2006 May;2(5):252-61. doi: 10.1038/ncprheum0165.
• Gaubitz M, Schorat A, Schotte H, Kern P, Domschke W. Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Lupus. 1999;8(9):731-6. doi: 10.1191/096120399678840927.
• Willeke P, Schotte H, Schluter B, Erren M, Becker H, Dyong A, Mickholz E, Domschke W, Gaubitz M. Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjogren's syndrome. Ann Rheum Dis. 2003 Apr;62(4):359-62. doi: 10.1136/ard.62.4.359.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: October 10, 2007
• First Submitted That Met QC Criteria: October 10, 2007
• First Posted (Estimate): October 11, 2007

Study Record Updates

• Last Update Posted (Estimate): October 11, 2007
• Last Update Submitted That Met QC Criteria: October 10, 2007
• Last Verified: August 1, 2004

More Information

Terms related to this study

• Keywords: Sjogren's syndrome; Mycophenolate sodium
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: myf-01-049