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

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

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

Study Overview

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

Detailed Description

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:

1. SS-1 may improve the clinical manifestation and quality of life for the patients with Sjögren's syndrome
2. To evaluate the effect of the Chinese medicine on the tongue diagnosis before and after treatment.
3. 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).
4. SS-1 may have the regulatory effect on cytokine secretion and immune function.
5. 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.
6. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hen-Hong Chang, M.D., Ph.D.; Phone Number: 2677 +886-3196200; Email: tcmchh55@gmail.com
• Study Contact Backup: Name: Ching-Mao Chang, M.D.; Phone Number: 2676 +886-3196200; Email: magicbjp@gmail.com

Study Locations

• Taiwan
  • Taoyuan
    • Gueishan Township, Taoyuan, Taiwan, 333
      • Recruiting
      • Center for Traditional Chinese Medicine, Taoyuan Chang Gung Memorial Hospital
      • Contact: Hen-Hong Chang, M.D., Ph.D.; Phone Number: 2677 +886-3196200; Email: tcmchh55@gmail.com
      • Sub-Investigator: Ching-Mao Chang, M.D.
      • 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.
      • Principal Investigator: Hen-Hong Chang, M.D.
      • Principal Investigator: Yeong-Jian Jan Wu Jan, M.D.
      • Principal Investigator: Ji-Yih Chen, M.D.
      • Principal Investigator: Yao-Fan Fang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• 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 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.; 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)	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

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
Liver, Kidney and Blood function monitor	Monitor the Liver, Kidney and Blood function (RBC, WBC, Hb, PLT, AST, ALT, BUN, Cre) of patient 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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: China Medical University, China; China Medical University Hospital; National Science Council, Taiwan; Chang Gung University
• Investigators: Principal Investigator: Hen-Hong Chang, M.D., Ph.D., Chang Gung University

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: April 1, 2014
• First Submitted That Met QC Criteria: April 7, 2014
• First Posted (Estimate): April 10, 2014

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: January 31, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Sjögren's syndrome; SS-1; Gan-Lu-Yin; Sang-Ju-Yin; Xuefu-Zhuyu-Decoction
• 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: 102-2481A

Plan for Individual participant data (IPD)

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