Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren's Syndrome

Study Overview
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Brief Summary
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To evaluate the modulation of immunity-related gene expression for the Sjögren's syndrome under Chinese herbal medicine (SS-1) treatment.

Detailed Description
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Objective: To evaluate the modulation of immunity-related gene expression for the Sjögren's syndrome under Chinese herbal medicine (SS-1) treatment. Method: The evidence of the regulation of oxidative-related cytokines and the antioxidant capacity could be provided from the previous randomized, double-blinded, placebo-controlled, cross-over design, two-center clinical trial for evaluating the effect of Chinese herbal medicine (SS-1) for the Sjögren's syndrome patients. However, the clinical trail could not find out the modulation of immunity-related gene expression for SS-1 treatment, and it did set up a healthy control group for SS-1 comparison. This study want to establish a healthy control group for evaluating the normal range of oxidative stress and cytokines, which this work could be used to compare with the 72 SS-1 subjects in previous study. And This study also want to analyze the 770 immunity-related gene expression for the Sjögren's syndrome under the SS-1 treatment: (1) The best 20 (at least) efficacy SJS subjects who were evaluated before and after SS-1 treatments. (2) The 10 (at least) healthy control subjects. The findings could provide the evidence on the modulation of immunity-related gene expression for clinical manifestation, oxidative stress and cytokine in Sjögren's syndrome patients. Expected Results: Establish the normal range of oxidative stress and cytokines for healthy control group. To evaluate the regulatory effect on oxidative stress and cytokine secretion between SS-1 group and healthy control group. To evaluate the immunity-related gene expression for the Sjögren's syndrome under the SS-1 treatment. To evaluate the immunity-related gene expression among the best efficacy SJS subjects and healthy control subjects. To evaluate the immunity-related gene expression with the characteristic of TCM tongue diagnosis. To analyze the correlation among clinical manifestations, Sjögren's syndrome -related clinical questionnaires and immunity-related gene expression.

Official Title
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Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren's Syndrome

Conditions
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Sjögren's Syndrome

Intervention / Treatment
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* Drug: SS-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary or Secondary Sjögren's syndrome patient Age from 20 to 75 year old, male or female patient Fit the criteria of 2002 year American-European classification If the subject took Cyclosporine, Cevimeline, Pilocarpine, Rituximab or other biological agent before enter into our study, the subject need to stop these drugs for one month If the subject took Gan-Lu-Yin, Sang- Ju-Yin or Xuefu-Zhuyu-Decoction before enter into our study, the subject need to stop these drugs for one month Secondary Sjögren's syndrome patient: Stable treatment: Steroid (≦10mg/d) and fixed hydroxychloroquine dose before 3 months enrolled No abnormal change of immunology, liver, kidney, and blood function No major life threatened condition Exclusion Criteria: Alcohol abuse, DM (Glucose PC>200mg/dL) and major life threatened condition Pregnancy or breast feeding Abnormal liver and kidney function Forbid steroid pulse therapy before 3 months enrolled into our study, and forbid the Chinese herbal medicine except SS-1

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SS-1<br>SS-1 is composed of the powder of Gan-Lu-Yin, Sang-Ju-Yin and Xuefu-Zhuyu-Decoction with the ratio of 2:1:1. Patients take 6 gram of experiment medicine three times per day. | Drug: SS-1<br>* The patients will be divided into two groups (A and B) at random and all of them keep the routine treatment in the rheumatology OPD. Group A patients will receive 12 weeks SS-1 treatment first, and then stop the SS-1 for 4 weeks for wash-out phase, and then receive 12 weeks placebo treatment. Group B patients receive 12 weeks placebo first, and then stop the placebo treatment for 4 weeks for wash-out phase, and then receive 12 weeks SS-1 treatment. SS-1 is composed of 3 traditional Chinese herbal formula: Gan-Lu-Yin, Sang-Ju-Yin and Xuefu-Zhuyu-Decoction with the ratio of 2:1:1. The placebo is composed with corn starch, pigment and minimal dose of 1% SS-1. Patients in both groups take 6 gram of SS-1/Placebo three times per day.<br>* Other names: Gan-Lu-Yin, Sang-Ju-Yin and Xuefu-Zhuyu-Decoction;|
| Placebo Comparator: Placebo<br>The placebo is composed of corn starch, pigment and minimal dose of 1% SS-1. Patients take 6 gram of experiment medicine three times per day. | Drug: Placebo<br>* The placebo is composed of corn starch, pigment and minimal dose of 1% SS-1. Patients take 6 gram of experiment medicine three times per day.<br>* Other names: 1% SS-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular surface disease index (OSDI) | OSDI is an questionnaire of dry eye. | 7 months | 
| EULAR Sjogren's syndrome patient reported index (ESSPRI) | ESSPRI is an questionnaire of dry, pain and fatigue. | 7 months | 
| Sjogren's syndrome symptoms Questionnaire | Sjogren's syndrome symptoms Questionnaire is an questionnaire of dry month. | 7 months | 
| Schirmer's test | Schirmer's test is an objective detection of dry eye, which this test use paper strips inserted into the eye for 5 minutes to measure the production of tears. | 7 months | 
| Salivary scintigraphy | Salivary scintigraphy is an objective detection of dry month, which is used to detect the salivary flow in parotid gland of Sjogren's syndrome. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress and antioxidant capacity | To evaluate the effect of the SS-1 on the oxidative stress and antioxidant capacity. The relative ratio is the unit of these biomarkers for oxidative stress and antioxidant capacity | 7 months | 
| Quality of life (SF-36) |  | 7 months | 
| Regulatory effect on cytokine | To evaluate the effect of the SS-1 on the cytokine. The pg/ml is the unit of these biomarkers for oxidative stress and antioxidant capacity | 7 months | 
| Nanostring nCounter immune Panel | To evaluate the effect of the SS-1 on the immunity-related gene expression. Nanostring nCounter immune Panel is a tool for detecting the immunity-related gene expression. | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sjögren's syndrome, Gan-Lu-Yin, Sang-Ju-Yin, Xuefu-Zhuyu-Decoction, Oxidative stress, Immune regulation, Gene modulation, SS-1