Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2013, Vol. 11 ›› Issue (6): 428-434.doi: 10.3736/jintegrmed2013059

• Study Protocol • Previous Articles    

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: Study protocol of a multicenter randomized controlled trial

Jian Liu(), Chuan-bing Huang, Yuan Wang, Gui-qin Xu, Yuan-yuan Cheng, Yun-xia Feng, Lei Liu, Ya-jun Qi   

  1. Department of Rheumatology, the First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
  • Received:2013-11-01 Accepted:2013-11-05 Online:2013-11-10 Published:2013-11-15


Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA.

Methods and design

This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1:1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo (imitation leflunomide). The control group will receive leflunomide and an herbal placebo (imitation Xinfeng Capsule). The American College of Rheumatology (ACR) Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate (ACR20), which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment.


The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA.

Trial registration

This trial has been registered in The identifier is NCT01774877.

Key words: Xinfeng Capsule, Rheumatoid arthritis, Double-blind method, Placebos, ACR criteria, Quality of life, Randomized controlled trials, Clinical protocols


Figure 1

Procedure of this studyAccording to the clinical manifestations, RA belongs to the category known as Bi Syndrome in CM terminology[30]. CM is a complete medical system with that has been in continuous practice for over 3 000 years[31], during which time it has been widely used for RA treatment[32]. But there lacks high-quality, modern scientific evidence that demonstrates efficacy and safety of CM in the treatment of RA."

[1] Gibofsky A . Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis[J]. Am J Manag Care, 2012,18(13 Suppl):s295-s302
[2] Chopra A, Abdel-Nasser A . Epidemiology of rheumatic musculoskeletal disorders in the developing world[J]. Best Pract Res Clin Rheumatol, 2008,22(4):583-604
doi: 10.1016/j.berh.2008.07.001
[3] Evans S, Cousins L, Tsao JC, Subramanian S, Sternlieb B, Zeltzer LK . A randomized controlled trial examining Iyengar yoga for young adults with rheumatoid arthritis: a study protocol[J]. Trials, 2011,12:19
doi: 10.1186/1745-6215-12-19
[4] McInnes IB, Schett G . The pathogenesis of rheumatoid arthritis[J]. N Engl J Med, 2011,365(23):2205-2219
doi: 10.1056/NEJMra1004965
[5] Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW , O’Dell J, Winthrop KL, Beukelman T, Bridges SL, Jr., Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis[J]. Arthritis Care Res (Hoboken), 2012,64(5):625-639
doi: 10.1002/acr.21641
[6] Sehgal VN, Verma P . Leflunomide: dermatologic perspective[J]. J Dermatolog Treat, 2013,24(2):89-95
doi: 10.3109/09546634.2011.595383
[7] Yoo HG, Yu HM, Jun JB, Jeon HS, Yoo WH . Risk factors of severe infections in patients with rheumatoid arthritis treated with leflunomide[J]. Mod Rheumatol, 2013,23(4):709-715
doi: 10.3109/s10165-012-0716-8
[8] Zhang C, Jiang M, Lu AP . Evidence-based Chinese medicine for rheumatoid arthritis[J]. J Tradit Chin Med, 2011,31(2):152-157
doi: 10.1016/S0254-6272(11)60031-9
[9] Liu J, Liu RL . The potential role of Chinese medicine in ameliorating extra-articular manifestations of rheumatoid arthritis[J]. Chin J Integr Med, 2011,17(10):735-737
doi: 10.1007/s11655-011-0872-2
[10] Cao YX, Liu J, Zhu Y . Effect of xinfeng capsule on the cardiac function in patients with rheumatoid arthritis[J]. Chin J Integr Med, 2011,17(10):738-743
doi: 10.1007/s11655-011-0873-1
[11] Feng Y, Liu J, Cheng Y, Wan L . Protective mechanism of XinFeng capsule on Sj?gren syndrome rat pulmonary function based on the TGF-beta1-ERK1 signal pathway[J]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2013,29(2):118-122
[12] Wan L, Liu J, Huang C, Wang Y, Shen X, Zhang W, Wang G, Fan H, Ge Y, Chen R, Cao Y, Zong R, Lei L . Effects of Xinfeng Capsule on pulmonary function based on treg-mediated notch pathway in a rat model of adjuvant arthritis[J]. J Tradit Chin Med, 2012,32(3):430-436
doi: 10.1016/S0254-6272(13)60050-3
[13] Rui-Kai Z, Jian L . Effects of Xinfeng capsules on expression of platelet granule membrane protein 140 and platelet cluster of differentiation 40 ligand in peripheral blood of adjuvant arthritis rats[J]. Int J Rheumatol, 2012,2012:139696
[14] Liu L, Zheng ZJ, Fang ZH . Experimental study on effect of xinfeng capsule in treating rats’ adjuvant arthritis on ultrastructure of synoviocyte and splenic lymphocyte[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2001,21(12):917-919
[15] Wan L, Liu J, Huang CB, Wang Y, Shen X, Zhang WD, Wang GZ, Fan HX, Ge Y, Chen RL, Cao YX, Zong RK . Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced arthritis and its mechanism[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2013,42(4):418-425
[16] Liu J, Yu XF, Zong RK . Effects of Xinfeng Capsule on behaviors and myocardial ultrastructure in adjuvant arthritis rats[J]. J Chin Integr Med, 2008,6(6):606-610
doi: 10.3736/jcim
[17] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT , Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G.2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Arthritis Rheum, 2010,62(9):2569-2581
doi: 10.1002/art.27584
[18] American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update[J]. Arthritis Rheum, 2002,46(2):328-346
doi: 10.1002/(ISSN)1529-0131
[19] Bruce B, Fries JF . The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation[J]. J Rheumatol, 2003,30(1):167-178
[20] Zhang M. Handbook of rating scales in psychiatry[M]. Changsha: Changsha Science and Technology Press, 2003,35, 39
[21] Ortiz Z, Shea B, Garcia Dieguez M, Boers M, Tugwell P, Boonen A, Wells G . The responsiveness of generic quality of life instruments in rheumatic diseases. A systematic review of randomized controlled trials[J]. J Rheumatol, 1999,26(1):210-216
[22] Bao C, Chen S, Gu Y, Lao Z, Ni L, Yu Q, Xu J, Li X, Liu J, Sun L, He P, Ma J, Xu S, Ding C . Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial[J]. Chin Med J (Engl), 2003,116(8):1228-1234
[23] Wang J. Clinical epidemiology — design, measurement and evaluation[M]. Shanghai: Shanghai Science and Technology Press, 2009,165
[24] Xiong NN, Zou JD, Jiang M . A design for a randomized protocol of multicenter clinical trial[J]. Zhong Yao Xin Yao Yu Lin Chuang Yao Li, 2002,13(5):321-323, 341
[25] Li Y, Zheng H, Zeng F, Zhou SY, Zhong F, Zheng HB, Chen M, Jing XH, Cai YY, Jia BH, Zhu B, Liu ZS . Use acupuncture to treat functional constipation: study protocol for a randomized controlled trial[J]. Trials, 2012,13:104
doi: 10.1186/1745-6215-13-104
[26] Yu XQ, Li JS, Li SY, Xie Y, Wang MH, Zhang HL, Wang HF, Wang ZW . Functional and psychosocial effects of pulmonary Daoyin on patients with COPD in China: study protocol of a multicenter randomized controlled trial[J]. J Integr Med, 2013,11(2):140-146
doi: 10.3736/jintegrmed2013015
[27] Xu WD, Zhang M, Feng CC, Yang XK, Pan HF, Ye DQ . IL-32 with potential insights into rheumatoid arthritis[J]. Clin Immunol, 2013,147(2):89-94
doi: 10.1016/j.clim.2013.02.021
[28] Hu PF, Chen Y, Cai PF, Jiang LF, Wu LD . Sphingosine-1-phosphate: a potential therapeutic target for rheumatoid arthritis[J]. Mol Biol Rep, 2011,38(6):4225-4230
doi: 10.1007/s11033-010-0545-9
[29] Schiff M, Peura D . HZT-501(DUEXIS?; ibuprofen 800 mg/famotidine 26.6 mg) gastrointestinal protection in the treatment of the signs and symptoms of rheumatoid arthritis and osteoarthritis[J]. Expert Rev Gastroenterol Hepatol, 2012,6(1):25-35
doi: 10.1586/egh.11.88
[30] Zhang EQ . Bi syndrome(Arthralgia Syndrome)[J]. J Tradit Chin Med, 2010,30(2):145-152
doi: 10.1016/S0254-6272(10)60032-5
[31] Wang ZZ, Fang YF, Wang Y, Mu FX, Chen J, Zou QH, Zhong B, Li JY, Bo GP, Zhang RH . Logistic regression analysis of damp-heat and cold-damp impeding syndrome of rheumatoid arthritis: a perspective in Chinese medicine[J]. Chin J Integr Med, 2012,18(8):575-581
doi: 10.1007/s11655-012-1172-1
[32] Jiang M, Zha Q, He Y, Lu A . Risk factors of gastrointestinal and hepatic adverse drug reactions in the treatment of rheumatoid arthritis with biomedical combination therapy and Chinese medicine[J]. J Ethnopharmacol, 2012,141(2):615-621
doi: 10.1016/j.jep.2011.07.026
[33] Zhang J, Ma YZ, Shen XM . Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson’s disease: study protocol of a multicenter, open-label, randomized active-controlled trial[J]. J Integr Med, 2013,11(4):285-290
doi: 10.3736/jintegrmed2013035
[1] Ju-Yeon Park, Young-Won Kwon, Sun-Ah Kim, Sun-Dong Park, Chang-Hyun Kim, Jin-Hee Kim, Ju-Hee Lee. Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-II collagen-induced arthritis. Journal of Integrative Medicine, 2021, 19(3): 265-273.
[2] Gerli E.G. Herr, Fábio Goulart da Silva, Francisco José Cidral-Filho, Fabricia Petronilho, Lucinéia Gainski Danielski, Mariana Pereira de Souza Goldim, Afonso Shiguemi Inoue Salgado, Franciane Bobinski, Daniel Fernandes Martins, Eliane R. Winkelmann. Effects of the use of bioceramic wraps in patients with lower limb venous ulcers: A randomized double-blind placebo-controlled trial. Journal of Integrative Medicine, 2020, 18(1): 27-.
[3] Goulnar Kasymjanova, Anh-Thi Tran, Victor Cohen, Carmela Pepe, Lama Sakr, David Small, Jason Scott Agulnik, Robert Thomas Jagoe. The use of a standardized Chinese herbal formula in patients with advanced lung cancer: A feasibility study. Journal of Integrative Medicine, 2018, 16(6): 390-395.
[4] Ching-Feng Su. Home care with acupuncture increased the quality of life in a patient with advanced cancer with neuropathic pain induced by bone metastasis: A case report. Journal of Integrative Medicine, 2018, 16(3): 208-210.
[5] Nobuari Takakura, Miho Takayama, Morihiro Nasu, Masako Nishiwaki, Akiko Kawase, Hiroyoshi Yajima . Patient blinding with blunt tip placebo acupuncture needles: Comparison between 1 mm and 2 mm skin press. Journal of Integrative Medicine, 2018, 16(3): 164-171.
[6] Zahra Hajmohammadi, Mojtaba Heydari, Majid Nimrouzi, Pouya Faridi, Mohammad Javad Zibaeenezhad, Gholamhossein Ranjbar Omrani, Mesbah Shams . Rhus coriaria L. increases serum apolipoprotein-A1 and high-density lipoprotein cholesterol levels: A double-blind placebo-controlled randomized clinical trial. Journal of Integrative Medicine, 2018, 16(1): 45-50.
[7] Hidetoshi Mori, Hiroshi Kuge, Shunji Sakaguchi, Tim Hideaki Tanaka, Junji Miyazaki. Determination of symptoms associated with hiesho among young females using hie rating surveys. Journal of Integrative Medicine, 2018, 16(1): 34-38.
[8] Molly J. Mallory, Alexander Do, Sara E. Bublitz, Susan J. Veleber, Brent A. Bauer, Anjali Bhagra. Puncturing the myths of acupuncture. Journal of Integrative Medicine, 2016, 14(5): 311-314.
[9] Maria T.Chao, AlexandraChang, SanjayReddy, James D.Harrison, JosephAcquah, MiriaToveg, TrilceSantana, Frederick M.Hecht. Adjunctive acupuncture for pain and symptom management in the inpatient setting: Protocol for a pilot hybrid effectiveness-implementation study. Journal of Integrative Medicine, 2016, 14(3): 228-238.
[10] Susana Seca, Sebastian Kirch, António S.Cabrita, Henry J.Greten. Evaluation of the effect of acupuncture on hand pain, functional deficits and health-related quality of life in patients with rheumatoid arthritis—A study protocol for a multicenter, double-blind, randomized clinical trial. Journal of Integrative Medicine, 2016, 14(3): 219-227.
[11] Paulo AraujoDias, André Brito Bastos Guimarães, Andrea de Oliveira Albuquerque, Karoline Lucasde Oliveira, Maria Luzete CostaCavalcante, Sergio BotelhoGuimarães. Short-term complementary and alternative medicine on quality of life in women with fibromyalgia. Journal of Integrative Medicine, 2016, 14(1): 29-35.
[12] Nouran A. Aleyeidi, Khaled S. Aseri, Shadia M. Matbouli, Albaraa A. Sulaiamani, Sumayyah A. Kobeisy. Effects of wet-cupping on blood pressure in hypertensive patients: A randomized controlled trial. Journal of Integrative Medicine, 2015, 13(6): 391-399.
[13] May To, Caroline Alexander. The effects of Park sham needles: A pilot study. Journal of Integrative Medicine, 2015, 13(1): 20-24.
[14] Zhong-liang Liu, Wei-rong Zhu, Wen-chao Zhou, Hai-feng Ying, Lan Zheng, Yuan-biao Guo, Jing-xian Chen, Xiao-heng Shen. Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: A systematic review and meta-analysis. Journal of Integrative Medicine, 2014, 12(4): 346-358.
[15] Zhi-yi Zhou, Ling Xu, He-gen Li, Jian-hui Tian, Li-jing Jiao, Sheng-fu You, Zhi-fen Han, Yi Jiang, Hui-ru Guo​, Hui Liu​. Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: Protocol for a randomized double-blind controlled trial. Journal of Integrative Medicine, 2014, 12(3): 175-181.
Full text



[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239