Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome

Study Overview
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Brief Summary
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To evaluate the efficacy of Chinese herbal medicine (SS-1) for the Sjögren's syndrome (SJS) patients.

Detailed Description
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Investigators take a randomized, double-blinded, placebo-controlled, cross-over design clinical trial to evaluate the effect of Chinese herbal medicine (SS-1) on the regulation of oxidative-related cytokines and the antioxidant capacity for the Sjögren's syndrome (SJS) patients. Through the oxidative stress reduction, the quality of life and clinical manifestation will be improved. Investigators will also use a SJS cell model to elucidate the antioxidant mechanism of SS-1. The SJS patients in this clinical trial will be screened and be referred from the out-patient department (OPD) of the Rheumatology Department of Chang Gung Memorial Hospital. 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 stop the SS-1 for 4 weeks to enter the wash-out phase, and then receive 12 weeks placebo treatment after the wash-out phase. Group B patients receive 12 weeks placebo first and stop the placebo treatment for 4 weeks to enter the wash-out phase, and then receive 12 weeks SS-1 treatment after the wash-out phase. 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 and the placebo is composed with corn starch, pigment and 1/100 SS-1. Patients in both groups take 6 gram of experiment medicine three times per day. Investigators plan to evaluate the associated parameters at the time just before treatment (V1), after treatment for 12 weeks (V2), at the end of wash-out phase (V3) and when the crossover treatment is completed (V4). Investigators use EULAR Sjogren's syndrome patient reported index, ocular surface disease index and SJS symptom questionnaire for clinical evaluation, and use the SF-36 for quality of life. And investigators use the schirmer's test, salivary scintigraphy, oxidative stress marker and related cytokine for objective observation. Expected Results: SS-1 may improve the clinical manifestation and quality of life for the patients with Sjögren's syndrome To evaluate the effect of the Chinese medicine on the tongue diagnosis before and after treatment. SS-1 may reduce the oxidative stress (8-OHdG and mtDNA 4977 bp deletion) and elevate the antioxidant capacity (TAC, GSH, mtDNA copy number, SOD, GPX, CAT). SS-1 may have the regulatory effect on cytokine secretion and immune function. SS-1 may have the capacity of reducing the oxidative stress, elevating the antioxidant capacity and regulating the immune response in the model of submaxillary salivary gland cell line with the induction of IFN-γand IFN-α. Identification of the single herb in the SS-1 mixture that regulates oxidative stress and cytokine in the model of submaxillary salivary gland cell line, and set up of the Chinese herbs screen platform for Sjögren's syndrome.

Official Title
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Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome - A Randomized Control Trial

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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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: 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 12weeks 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 12weeks 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) | SS-1 may improve the subjective observation of dry eye. | 7 months | 
| EULAR Sjogren's syndrome patient reported index (ESSPRI) | SS-1 may improve the subjective sensation of dry, pain and fatigue. | 7 months | 
| SJS symptoms Questionnaire | SS-1 may improve the subjective sensation of dry month. | 7 months | 
| Schirmer's test | SS-1 may improve the objective observation of dry eye. | 7 months | 
| Salivary scintigraphy | SS-1 may improve the objective observation of dry month. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress and antioxidant capacity | SS-1 may reduce the oxidative stress and elevate the antioxidant capacity | 7 months | 
| Quality of life (SF-36) | SS-1 may improve the subjective observation of quality of life. | 7 months | 
| Regulatory effect on cytokine | SS-1 may have the regulatory effect on cytokine secretion and immune function. | 7 months | 

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