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

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

Study Overview

• Status: Unknown
• Conditions: Sjögren's Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: SS-1

Detailed Description

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:

1. Establish the normal range of oxidative stress and cytokines for healthy control group.
2. To evaluate the regulatory effect on oxidative stress and cytokine secretion between SS-1 group and healthy control group.
3. To evaluate the immunity-related gene expression for the Sjögren's syndrome under the SS-1 treatment.
4. To evaluate the immunity-related gene expression among the best efficacy SJS subjects and healthy control subjects.
5. To evaluate the immunity-related gene expression with the characteristic of TCM tongue diagnosis.
6. To analyze the correlation among clinical manifestations, Sjögren's syndrome -related clinical questionnaires and immunity-related gene expression.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Gueishan Township, Taiwan, 333
    • Recruiting
    • Taoyuan Chang Gung Memorial Hospital
    • Principal Investigator: Yau-Huei Wei, Ph.D.
    • Principal Investigator: Jr-Rung Lin, Ph.D.
    • Principal Investigator: Kuang-Hui Yu, M.D.
    • Principal Investigator: Shue-Fen Luo, M.D.
    • Contact: Kuang-Hui Yu, M.D.; Email: goutyu@gmail.com
    • Sub-Investigator: Ching-Mao Chang, M.D., Ph.D.
  • Taichung, Taiwan, 404
    • Recruiting
    • China Medical University Hospital
    • Contact: Hen-Hong Chang, M.D., Ph.D.; Phone Number: 3501 +886-4-22053366; Email: tcmchh55@gmail.com
    • Contact: Ching-Mao Chang, M.D.; Phone Number: 886
    • Principal Investigator: Hen-Hong Chang, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SS-1; 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; 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.; Other Names: Gan-Lu-Yin, Sang-Ju-Yin and Xuefu-Zhuyu-Decoction
Placebo Comparator: Placebo; 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; 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.; Other Names: 1% SS-1

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effect (AE) and Adverse drug reaction(ADR)	Monitor the Adverse effect (AE) and Adverse drug reaction(ADR) during the SS-1 trial.	7 months
Traditional Chinese medicine (TCM) tongue diagnosis	To evaluate the effect of the SS-1 on the TCM tongue diagnosis before and after treatment.	7 months
Liver, Kidney and Blood function monitor	Monitor the Liver, Kidney and Blood function monitor (RBC, WBC, Hb, Platelet, AST, ALT, BUN, Cre) of patient during the SS-1 trial, and the different units are listed below: WBC (1000/uL), RBC (million/uL), Hb (g/dL), Platelet (1000/uL), AST (U/L), ALT (U/L), BUN (mg/dL), Serum Creatinine (mg/dL).	7 months

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: China Medical University, China; Chang Gung Memorial Hospital; National Research Program for Biopharmaceuticals, Taiwan
• Investigators: Study Chair: Hen-Hong Chang, M.D., Ph.D., China Medical University Hospital

Publications and helpful links

General Publications

• Chang CM, Chu HT, Wei YH, Chen FP, Wang S, Wu PC, Yen HR, Chen TJ, Chang HH. The Core Pattern Analysis on Chinese Herbal Medicine for Sjogren's syndrome: A Nationwide Population-Based Study. Sci Rep. 2015 Apr 29;5:9541. doi: 10.1038/srep09541. Erratum In: Sci Rep. 2015;5:14887. Sci Rep. 2017 May 25;7:46824.

Helpful Links

• NCT02110446: Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome (SS-1)

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Estimate): August 4, 2016
• Last Update Submitted That Met QC Criteria: August 1, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Oxidative stress; Sjögren's syndrome; SS-1; Gan-Lu-Yin; Sang-Ju-Yin; Xuefu-Zhuyu-Decoction; Gene modulation; Immune regulation
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: CMUH105-REC3-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED