Clinical trial NCT02691949: Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren's Syndrome
Official title: Efficacy and Safety of Mycophenolate Mofetil in subjectswithSjogren's Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sjogren's Syndrome
Lead sponsor: Kaohsiung Medical University
Sponsor class: OTHER
First posted: 2016-02-25
Enrollment: 54
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of Composite Index of Sjogren's syndrome
timeFrame: baseline, 28 week
Secondary outcomes:
measure: ocular dryness
timeFrame: baseline, 28 week
measure: physician visual analog scale (VAS)
timeFrame: baseline, 28 week
measure: Schirmer's test
timeFrame: baseline, 28 week
measure: Saxon's test
timeFrame: baseline, 28 week
measure: heart rate
timeFrame: baseline, 28 week
measure: blood pressure
timeFrame: baseline, 28 week
measure: leukocyte count
timeFrame: baseline, 28 week
measure: Hb level
timeFrame: baseline, 28 week
measure: platelet count
timeFrame: baseline, 28 week
Other outcomes:
Locations:
Study officials:
affiliation: Kaohsiung Medical University
name: Jeng-Hsien Yen
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaohsiung Medical University
name: Wen-Chan Tsai
role: STUDY_DIRECTOR
affiliation: Kaohsiung Medical University
name: Tsan-Teng Ou, MD
role: STUDY_DIRECTOR
affiliation: Kaohsiung Medical University
name: Cheng-Chin Wu, MD
role: STUDY_DIRECTOR
affiliation: Kaohsiung Medical University
name: Wan-Yu Sung, MD
role: STUDY_DIRECTOR
affiliation: Kaohsiung Medical University
name: Chia-Chun Tseng, MD
role: STUDY_DIRECTOR
References:
citation: 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.