Clinical trial NCT00542763: Mycophenolate Sodium Treatment in Patients With Primary Sjogren's Syndrome
Official title: Mycophenolate Sodium Treatment in Patients With Primary Sjogren's Syndrome - An Open Label Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Sjogren's Syndrome
Keywords: Sjogren's syndrome
Mycophenolate sodium
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-10-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of mycophenolate sodium for sicca syndrome and changes in laboratory values associated with the disease
timeFrame: Basline, week 12 and week 24
Secondary outcomes:
measure: Safety of mycophenolate sodium in patients with primary Sjogren's syndrome: Clinical examination, full blood count, renal function tests, liver function tests
timeFrame: basline, after week 4, 12, and week 24
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: University Hospital Muenster
state: NRW
Study officials:
affiliation: University Hospital Muenster
name: Markus Gaubitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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 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.
citation: 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.