Low-dose Interleukin-2 and Rapamycin on sjögren's Syndrome

Study Overview
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Brief Summary
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The purpose of this paper is to analysis of therapeutic effect and immunological mechanism of low-dose IL-2 combined with rapamycin in the treatment of Sjogren's syndrome

Detailed Description
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A randomized, open clinical trial was designed. Patients will be randomly divided into three groups，including Ld-IL2 group, rapamycin group, Ld-IL2+rapamycin group. The improvement of clinical and laboratory indexes will be evaluated. Changes of immune cell subsets and cytokines will be monitored.

Official Title
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Therapeutic Effect of Low Dose IL-2 Combined With Rapamycin in on sjögren's Syndrome

Conditions
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Sjögren's Syndrome

Intervention / Treatment
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* Drug: low-dose interleukin-2
* Drug: rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, and aged 18-70 at the time of screening visit. Patients with Sjogren's syndrome who meet the 2002 EULAR classification criteria. If the standardized treatment is not effective or relapses, it is clinically necessary to give additional immunomodulatory treatment. Disease activity: ESSDAI≥4 points. The pregnancy test results of female subjects of childbearing age should be negative at screening and baseline. The written informed consent form approved by the Ethics Committee of Peking University People's Hospital was signed and dated by the subject or legal representative. Exclusion Criteria: Severe chronic liver, kidney and heart dysfunction. Severe drug-resistant bacterial infections, such as bacteremia and septicemia. Patients with tumor and tumor history. Chronic respiratory failure. Patients who are ineffective in high-dose hormone pulse therapy. Those who use rituximab or other biological agents within 3 months. Patients with active tuberculosis infection or potential tuberculosis infection. There are obstacles that can't cooperate or cause interference in completing this research: such as mental patients.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Low-dose interleukin-2<br>One million IU of IL-2 was injected subcutaneously once every other day for 4 weeks. | Drug: low-dose interleukin-2<br>* low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10 6 IU once every other day, for 4 weeks.<br>* Other names: Recombinant Human Interleukin-2;|
| Active Comparator: Rapamycin<br>Rapamycin 0.5ml once per day for 4 weeks. | Drug: rapamycin<br>* Rapamycin 0.5ml was taken orally once per day<br>* Other names: sirolimus;|
| Experimental: Low-dose interleukin-2 and rapamycin<br>One million IU of IL-2 was injected subcutaneously once every other day and rapamycin 0.5ml once per day for 4 weeks. | Drug: low-dose interleukin-2<br>* low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10 6 IU once every other day, for 4 weeks.<br>* Other names: Recombinant Human Interleukin-2;Drug: rapamycin<br>* Rapamycin 0.5ml was taken orally once per day<br>* Other names: sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Treg cells in peripheral blood | Proportion of Treg cells in peripheral blood will be detected by flowcytometry | week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ESSDAI [potential score 0 - 123] | ESSDAI is [European League Against Rheumatism (EULAR) Sjögrens Syndrome Disease Activity Index]. Higher scores mean a worse outcome. | week 4 | 
| Physician's Global Disease Activity VAS, (potential score 0 - 10) | Physician's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Higher scores mean a worse outcome. | week 4 | 
| Patient's Global Disease Activity VAS, (potential score 0 - 80) | Patient's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Higher scores mean a worse outcome. | week 4 | 
| Rate of Participants with adverse effects associated with experimental drugs | Adverse effects include fever, rash, abnormal liver function, rate of new-onset infection and any abnormal measures associated with low-dose IL-2 therapy, and oral ulcer, rash, hypertension, anemia, arthralgia, diarrhea and any abnormal measures associated with rapamycin therapy. | week 4 |