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

• ClinicalTrials.gov Identifier: NCT02110446
• Recruitment Status: Unknown
• First Posted: April 10, 2014
• Last Update Posted: February 2, 2016
• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Chang Gung University; National Science Council, Taiwan; China Medical University, China; China Medical University Hospital
• Information provided by (Responsible Party): Chang Gung Memorial Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Sjögren's Syndrome	Drug: SS-1; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome - A Randomized Control Trial
• Study Start Date: February 2014
• Estimated Primary Completion Date: July 2016
• Estimated Study Completion Date: July 2016

Arms and Interventions

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 Name: 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 Name: 1% SS-1

Outcome Measures

Primary Outcome Measures :

1. Ocular surface disease index (OSDI) [ Time Frame: 7 months ]
   SS-1 may improve the subjective observation of dry eye.
2. EULAR Sjogren's syndrome patient reported index (ESSPRI) [ Time Frame: 7 months ]
   SS-1 may improve the subjective sensation of dry, pain and fatigue.
3. SJS symptoms Questionnaire [ Time Frame: 7 months ]
   SS-1 may improve the subjective sensation of dry month.
4. Schirmer's test [ Time Frame: 7 months ]
   SS-1 may improve the objective observation of dry eye.
5. Salivary scintigraphy [ Time Frame: 7 months ]
   SS-1 may improve the objective observation of dry month.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Adverse effect (AE) and Adverse drug reaction(ADR) [ Time Frame: 7 months ]
   Monitor the Adverse effect (AE) and Adverse drug reaction(ADR) during the SS-1 trial.
2. Liver, Kidney and Blood function monitor [ Time Frame: 7 months ]
   Monitor the Liver, Kidney and Blood function (RBC, WBC, Hb, PLT, AST, ALT, BUN, Cre) of patient during the SS-1 trial.
3. Traditional Chinese medicine (TCM) tongue diagnosis [ Time Frame: 7 months ]
   To evaluate the effect of the SS-1 on the TCM tongue diagnosis before and after treatment.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Hen-Hong Chang, M.D., Ph.D.; +886-3196200 ext 2677; tcmchh55@gmail.com

Contact: Ching-Mao Chang, M.D.; +886-3196200 ext 2676; magicbjp@gmail.com

Locations

Taiwan

Center for Traditional Chinese Medicine, Taoyuan Chang Gung Memorial Hospital; Recruiting

Gueishan Township, Taoyuan, Taiwan, 333

Contact: Hen-Hong Chang, M.D., Ph.D. +886-3196200 ext 2677 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.

Sponsors and Collaborators

Chang Gung Memorial Hospital

Chang Gung University

National Science Council, Taiwan

China Medical University, China

China Medical University Hospital

Investigators

• Principal Investigator: Hen-Hong Chang, M.D., Ph.D.; Chang Gung University

More Information

• Responsible Party: Chang Gung Memorial Hospital
• ClinicalTrials.gov Identifier: NCT02110446
• Other Study ID Numbers: 102-2481A
• First Posted: April 10, 2014
• Last Update Posted: February 2, 2016
• Last Verified: January 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Chang Gung Memorial Hospital:

Sjögren's syndrome; SS-1; Gan-Lu-Yin; Sang-Ju-Yin; Xuefu-Zhuyu-Decoction

Additional relevant MeSH terms:

Sjogren's Syndrome; Syndrome; Disease; Pathologic Processes; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases