|- candidate number||2752|
|- NTR Number||NTR1099|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||18-sep-2007|
|- Secondary IDs||N/A |
|- Public Title||Observational study;|
Mycophenolate sodium (Myfortic) in primary Sjogren’s syndrome.
|- Scientific Title||OBSERVATIONAL STUDY;|
MYCOPHENOLATE SODIUM TREATMENT IN PATIENTS WITH PRIMARY SJOGREN’S SYNDROME – A PILOT TRIAL.
|- hypothesis||Mycophenolate is a selective inhibitor of inosine-monophosphate-dehydrogenase which leads to inhibition of the de novo pathway of nucleotide synthesis. The antiproliferative effect of mycophenolate 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 primary Sjogren's syndrome, mycophenolate might be a promising agent in the treatment of pSS.
|- Healt Condition(s) or Problem(s) studied||Sjogren's syndrome|
|- Inclusion criteria||1. Diagnosis of primary Sjogren's syndrome based on the American-European Consensus criteria (Vitali et al.);|
2. Erythrocyte sedimentation rate >25mm/h and hypergammaglobulinemia (>1500 mg/dl);
3. Presence of anti-SS-A and /or SS-B antibodies and/or rheumatoid factor;
4. Requirement of artificial teardrops due to symptomatic sicca syndrome;
5. Adequate contraception for females of childbearing potential;
6. Inadequate response or intolerance of prior treatment with hydroxychloroquine and/or azathioprine.
|- Exclusion criteria||1. Age below 18 or above 75 years;|
2. Pregnant or lactating women;
3. Secondary Sjogren’s syndrome;
4. History of cancer, severe infections or other uncontrolled diseases;
5. Treatment with concomitant disease modifying anti-rheumatic drugs within the least 4 weeks before baseline evaluation;
6. Prednisolone dose of >5mg/d or changes of prednisolone dose within the least 4 weeks before baseline;
7. Use of secretagogues (e.g. pilocarpine, civemeline) or medications that potentially diminish exocrine gland function (e.g. tricyclic antidepressants, anti-cholinergic drugs).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||3-apr-2005|
|- planned closingdate||1-apr-2007|
|- Target number of participants||11|
|- Interventions||The dosage of mycophenolate sodium shoud increase weekly by 360mg up to a maximum stable dose of 1440 mg daily. In patients not well tolerating the drug the dosage can be reduced to 720 mg per day.
Follow up visits will be after 4 week, |
12 weeks and 24 weeks
|- Primary outcome||To evaluate the efficacy of mycophneolate sodium treatment in patients with pSS refractory to other immunosuppressive agents. |
Glandular function tests, questionnaires, and laboratory tests at baseline, after 4 weeks, week 12, at week 24.
The lachrymal gland function will be assessed by unanesthetized Schirmer’s test.
In addition, we will collected and weighed the unstimulated whole saliva throughout 5 minutes.
Visual analoge scale for the severity of ocular dryness, arthralgia, and fatigue on a 100-mm visual analogue scale (VAS) ranging from 0 to 100.
Outcome will also be determined by the Short Form-36 (SF-36). In addition, the Health Assessment Questionnaire (HAQ) has to be completed
Levels of immunoglobulins (IgG, IgM and IgA), RF-IgM as well as serum concentrations of complement levels (C3 and C4) will be measured during the trial. Also IgG antibodies to SS-A and SS-B will be analysed.
|- Secondary outcome||Safety of mycophenolate sodium treatment in patients with pSS: |
History-taking including, clinical examination.
At each clinical visit, the patients will be asked about possible adverse events.
Laboratory tests at baseline, after 4 weeks, week 12, at week 24.(i.e. ESR, C-reactive protein (CRP), renal and liver function tests, total protein, and full blood count).
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Dr. Peter Willeke|
|- CONTACT for SCIENTIFIC QUERIES||Dr. Peter Willeke|
|- Sponsor/Initiator ||Muenster University Clinic|
(Source(s) of Monetary or Material Support)
|Novartis Pharma GmbH, Nürnberg, Germany|
|- Publications||1. 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, 8:731-736;|
2. Willeke P, Domschke W, Gaubitz M: Mycophenolate Mofetil for the treatment of primary Sjögren's Syndrome: A case report. Ann Rheum Dis 2003, 62 (Suppl. 1) :352;
3. Mavragani CP, Moutsopoulos NM, Moutsopoulos HM: The management of Sjogren's syndrome.
Nat Clin Pract Rheumatol 2006, 2:252-261.
|- 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. |
Since activation of lymphocytes is a key element in the pathogenesis of the disease inhibition of lymphocyte activation might be beneficial in the treatment of pSS. Mycophenolic acid has anti-proliferative effects on B- and T-cells.
Mycophenolate containing compounds such as mycophenolate mofetil (MMF) and enteric coated mycophenolate sodium (MPS) are immunosuppressive drugs approved for the prevention of transplant rejection. MPS 720 mg and MMF 1000 mg deliver nearly equimolar doses of the active immunosuppressive agent.
Although no controlled study has been performed so far mycophenoate has been suggested as sole or adjuvant treatment for primary Sjogren's syndrome pSS in a recent review articles.
The recent observations and the immunosuppressive effect of mycopenolate sodium in other autoimmune diseases led us to evaluate the efficacy and safety of Mycophenolate sodium treatment in patients with pSS refractory to other immunosuppressive agents.
|- Main changes (audit trail)|
|- RECORD||18-sep-2007 - 24-nov-2009|