Mycophenolate Sodium Treatment in Patients With Primary Sjogren's Syndrome

Primary Sjogren's Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00542763
• Other study ID #: myf-01-049
• Status: Completed
• Phase: Phase 1
• First received: October 10, 2007
• Last updated: October 10, 2007
• Start date: April 2005
• Est. completion date: September 2007

Study information

• Verified date: August 2004
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Primary Sjogren's Syndrome
• Sjogren's Syndrome
• Syndrome

Intervention

Drug:
• Mycophenolate sodium
Medical treatment is initiated with one tablet of 360 mg mycophenolate sodium orally per day for eligible patient. The dosage will be increased weekly by 360 mg up to a maximum stable dose of 1440mg daily. In patients not well tolerating the drug the dosage can be reduced to 720 mg per day.

Locations

Country	Name	City	State
Germany	University Hospital Muenster	Muenster	NRW

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Muenster	Novartis

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View Citation

Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjögren's syndrome. Nat Clin Pract Rheumatol. 2006 May;2(5):252-61. Review. — View Citation

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 Sjögren's Syndrome. Classification criteria for Sjögren'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. Review. — View Citation

Willeke P, Domschke W, Gaubitz M: Mycophenolate Mofetil for the treatment of primary Sjogren's Syndrome: A case report. Ann Rheum Dis, 62 (Suppl. 1):352,2003

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of mycophenolate sodium for sicca syndrome and changes in laboratory values associated with the disease		Basline, week 12 and week 24
Secondary	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