Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren'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 mofetil could be used to improve ocular dryness and oral dryness in patients with Sjogren's syndrome.

Study Overview

• Status: Unknown
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Drug: Mycophenolate mofetil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of primary Sjogren's syndrome based on the 2002 American-European Consensus criteria
2. Aged 20 to 75 years
3. Stable doses of oral corticosteroids(≦5mg/d) for at least 4 weeks before enrollment

4. Intolerance or inadequate response to hydroxychloroquine and (pilocarpine or cevimeline), defined as less than 50mm on at least 2 of VAS including:

   1. global assessment : 0mm (very bad) to 100mm (very good)
   2. pain: 0mm (very bad) to 100mm (very good)
   3. fatigue: 0mm (very bad) to 100mm (very good)
   4. xerostomia: 0mm (very bad) to 100mm (very good)
5. Adequate contraception for patients of childbearing potential

Exclusion Criteria:

1. 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

2. Any one of laboratory abnormalities:

   1. Serum creatinine ≥2 mg/dl
   2. aspartate aminotransferase (AST) or alanine transaminase (ALT) more than 1.5 x upper normal range of the laboratory
   3. Leukopenia (WBC<4000/μl)
   4. Hb ≤ 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
   5. Neutrophil less than 1.5 x 109/l
   6. Platelet count less than 150 x 109/l
3. History of other autoimmune diseases
4. Use topical cyclosporine eyedrops, antihistamine, anticholinergic, antidepressant, or antipsychotic drug with possible effects on ocular dryness or oral dryness within 1 month
5. Pregnant or lactating women
6. Previous or current malignancies adequately controlled less than 5 years, hepatitis B, hepatitis C, HIV infection, tuberculosis, or diabetes
7. Subjects with serious infections requiring hospitalization within the last 12 months
8. Subjects with herpes zoster or cytomegalovirus that resolved less than 2 months before enrollment
9. Subjects who have received any live vaccines within 3 months
10. 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
11. History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infection
12. Subjects who are impaired, incapacitated, or incapable of completing study-related assessments
13. History of allergy to mycophenolate sodium
14. Nausea, vomiting, diarrhea within 1 week before enrollment
15. History of psychosis, seizure, retinopathy
16. Infection 2 weeks before enrollment
17. Heart rate < 60/min at rest

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Kaohsiung Medical University
• Investigators: Principal Investigator: Jeng-Hsien Yen, Kaohsiung Medical University; Study Director: Wen-Chan Tsai, Kaohsiung Medical University; Study Director: Tsan-Teng Ou, MD, Kaohsiung Medical University; Study Director: Cheng-Chin Wu, MD, Kaohsiung Medical University; Study Director: Wan-Yu Sung, MD, Kaohsiung Medical University; Study Director: Chia-Chun Tseng, MD, Kaohsiung Medical University

Publications and helpful links

General Publications

• Willeke P, Schluter B, Becker H, Schotte H, Domschke W, Gaubitz M. Mycophenolate sodium treatment in patients with primary Sjogren syndrome: a pilot trial. Arthritis Res Ther. 2007;9(6):R115. doi: 10.1186/ar2322.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: February 16, 2016
• First Submitted That Met QC Criteria: February 24, 2016
• First Posted (Estimate): February 25, 2016

Study Record Updates

• Last Update Posted (Estimate): September 23, 2016
• Last Update Submitted That Met QC Criteria: September 21, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• 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: S10418-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We won't share our data