Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren's Syndrome

Last updated: September 21, 2016
Sponsor: Kaohsiung Medical University
Overall Status: Trial Status Unknown

Phase

2

Condition

Sjogren's Syndrome

Dermatomyositis (Connective Tissue Disease)

Treatment

N/A

Clinical Study ID

NCT02691949
S10418-4
  • Ages 20-75
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Diagnosis of primary Sjogren's syndrome based on the 2002 American-European Consensuscriteria

  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 orcevimeline), defined as less than 50mm on at least 2 of VAS including:

  5. global assessment : 0mm (very bad) to 100mm (very good)

  6. pain: 0mm (very bad) to 100mm (very good)

  7. fatigue: 0mm (very bad) to 100mm (very good)

  8. xerostomia: 0mm (very bad) to 100mm (very good)

  9. Adequate contraception for patients of childbearing potential

Exclusion

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:

  3. Serum creatinine ≥2 mg/dl

  4. aspartate aminotransferase (AST) or alanine transaminase (ALT) more than 1.5 xupper normal range of the laboratory

  5. Leukopenia (WBC<4000/μl)

  6. Hb ≤ 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females

  7. Neutrophil less than 1.5 x 109/l

  8. Platelet count less than 150 x 109/l

  9. History of other autoimmune diseases

  10. Use topical cyclosporine eyedrops, antihistamine, anticholinergic, antidepressant, orantipsychotic drug with possible effects on ocular dryness or oral dryness within 1month

  11. Pregnant or lactating women

  12. Previous or current malignancies adequately controlled less than 5 years, hepatitis B,hepatitis C, HIV infection, tuberculosis, or diabetes

  13. Subjects with serious infections requiring hospitalization within the last 12 months

  14. Subjects with herpes zoster or cytomegalovirus that resolved less than 2 months beforeenrollment

  15. Subjects who have received any live vaccines within 3 months

  16. Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal,haematological or neurological conditions, chronic or latent infectious diseases orimmune deficiency which places the patient at an unacceptable risk for participationin the study

  17. History of recurring or chronic infections or underlying conditions which may furtherpredispose patients to serious infection

  18. Subjects who are impaired, incapacitated, or incapable of completing study-relatedassessments

  19. History of allergy to mycophenolate sodium

  20. Nausea, vomiting, diarrhea within 1 week before enrollment

  21. History of psychosis, seizure, retinopathy

  22. Infection 2 weeks before enrollment

  23. Heart rate < 60/min at rest

Study Design

Total Participants: 54
Study Start date:
February 01, 2016
Estimated Completion Date:
April 30, 2018

Study 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.