Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren's Syndrome

Study Overview
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Brief Summary
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Past literature showed encouraging effects of mycophenolate on dryness symptoms and quality of life in patients with Sjogren's syndrome. Mycophenolate also has excellent immunomodulation effects in lupus nephritis. Currently Mycophenolate is only used in lupus nephritis and organ transplant. It is unknown whether low dosage of mycophenolate mofetil could be used to improve ocular dryness and oral dryness in patients with Sjogren's syndrome.

Detailed Description
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Sjogren's syndrome is one of the most common autoimmune diseases in Taiwan. It is characterized by keratoconjunctivitis sicca and xerostomia. Although it is well established that Sjogren's syndrome is caused by infiltration and destruction of lacrimal gland and salivary gland by lymphocytic cells, effective treatment of patients' symptoms is lacking. Hydroxychloroquine is the most well-studied medication in Sjogren's syndrome. However, recent clinical trials showed disappointing effects of hydroxychloroquine in Sjogren's syndrome. Thus there is an unmet need to find effective treatment for patient's bothering symptoms. Mycophenolate is a selective inhibitor of inosinemonophosphate 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 with other eukaryotic cells. Since these lymphocytes have been suggested to play a pivotal role in the inflammation and immunopathogenesis of Sjogren's syndrome, mycophenolate might be a promising agent in the treatment of Sjogren's syndrome. Past literature showed encouraging effects of mycophenolate on dryness symptoms and quality of life in patients with Sjogren's syndrome. Mycophenolate also has excellent immunomodulation effects in lupus nephritis. Currently mycophenolate is only used in lupus nephritis and organ transplant. It is unknown whether low dosage of mycophenolate could be used to improve ocular dryness and oral dryness in patients with Sjogren's syndrome.

Official Title
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Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren's Syndrome

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Drug: Mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary Sjogren's syndrome based on the 2002 American-European Consensus criteria Aged 20 to 75 years Stable doses of oral corticosteroids(≦5mg/d) for at least 4 weeks before enrollment Intolerance or inadequate response to hydroxychloroquine and (pilocarpine or cevimeline), defined as less than 50mm on at least 2 of VAS including: global assessment : 0mm (very bad) to 100mm (very good) pain: 0mm (very bad) to 100mm (very good) fatigue: 0mm (very bad) to 100mm (very good) xerostomia: 0mm (very bad) to 100mm (very good) Adequate contraception for patients of childbearing potential Exclusion Criteria: Receiving biologics during the 6 previous months or any other immunosuppressant (methotrexate, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil (MMF), mycophenolate sodium, leflunomide, penicillamine) during the previous month Any one of laboratory abnormalities: Serum creatinine ≥2 mg/dl aspartate aminotransferase (AST) or alanine transaminase (ALT) more than 1.5 x upper normal range of the laboratory Leukopenia (WBC<4000/μl) Hb ≤ 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females Neutrophil less than 1.5 x 109/l Platelet count less than 150 x 109/l History of other autoimmune diseases Use topical cyclosporine eyedrops, antihistamine, anticholinergic, antidepressant, or antipsychotic drug with possible effects on ocular dryness or oral dryness within 1 month Pregnant or lactating women Previous or current malignancies adequately controlled less than 5 years, hepatitis B, hepatitis C, HIV infection, tuberculosis, or diabetes Subjects with serious infections requiring hospitalization within the last 12 months Subjects with herpes zoster or cytomegalovirus that resolved less than 2 months before enrollment Subjects who have received any live vaccines within 3 months Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal, haematological or neurological conditions, chronic or latent infectious diseases or immune deficiency which places the patient at an unacceptable risk for participation in the study History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infection Subjects who are impaired, incapacitated, or incapable of completing study-related assessments History of allergy to mycophenolate sodium Nausea, vomiting, diarrhea within 1 week before enrollment History of psychosis, seizure, retinopathy Infection 2 weeks before enrollment Heart rate < 60/min at rest

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mycophenolate mofetil standard<br>mycophenolate mofetil 250mg 2# twice per day (BID) | Drug: Mycophenolate mofetil<br>* mycophenolate mofetil 1# BID-2# BID<br>|
| Experimental: Mycophenolate sodium low<br>mycophenolate mofetil 250mg 1# twice per day (BID) | Drug: Mycophenolate mofetil<br>* mycophenolate mofetil 1# BID-2# BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Composite Index of Sjogren's syndrome |  | baseline, 28 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ocular dryness | We will calculate the change of ocular dryness from baseline to week 28 (0mm [very bad] to 100mm [very good]) | baseline, 28 week | 
| physician visual analog scale (VAS) | We will calculate the change of physician VAS from baseline to week 28 (0mm [very bad] to 100mm [very good]) | baseline, 28 week | 
| Schirmer's test | We will calculate the change of Schirmer's test results from baseline to week 28 | baseline, 28 week | 
| Saxon's test | We will calculate the change of Saxon's test results from baseline to week 28 | baseline, 28 week | 
| heart rate | resting heart rate | baseline, 28 week | 
| blood pressure | resting blood pressure | baseline, 28 week | 
| leukocyte count | WBC count | baseline, 28 week | 
| Hb level | Hb level | baseline, 28 week | 
| platelet count | platelet count | baseline, 28 week |