Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

Linda L D Zhong, Chung Wah Cheng, Yawen Chan, King Hong Chan, Ting Wa Lam, Xiao Rui Chen, Chi Tak Wong, Justin C Y Wu, Zhao Xiang Bian, Linda L D Zhong, Chung Wah Cheng, Yawen Chan, King Hong Chan, Ting Wa Lam, Xiao Rui Chen, Chi Tak Wong, Justin C Y Wu, Zhao Xiang Bian

Abstract

Background: Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed.

Methods/design: This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects.

Discussion: This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future.

Trial registration: NCT01695850.

Figures

Figure 1
Figure 1
Participant flowchart.
Figure 2
Figure 2
Schedule of enrolment, intervention and assessments.

References

    1. Eoff JC. Optimal treatment of chronic constipation in managed care: review and roundtable discussion. J Manag Care Pharm. 2008;14:1–15.
    1. Cheng C, Chan AO, Hui WM, Lam SK. Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study. Aliment Pharmacol Ther. 2003;18:319–326. doi: 10.1046/j.1365-2036.2003.01663.x.
    1. Drossman DA, Corazziari E, Delvaux M, Spiller RC, Talley NJ, Thompson WG. Rome III: The Functional Gastrointestinal Disorders. McLean, VA: Degnon Associates; 2006.
    1. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100:936–971. doi: 10.1111/j.1572-0241.2005.40925.x.
    1. Youssef NN, Sanders L, Di Lorenzo C. Adolescent constipation: evaluation and management. Adolesc Med Clin. 2004;15:37–52. doi: 10.1016/j.admecli.2003.11.007.
    1. Zhang BY, Dong JH, Zhou ZY. Traditional Chinese Internal Medicine. Shang Hai: Shang Hai Science and Technology Press; 1985.
    1. Maclean W, Lyttleton J. Clinical Handbook of Internal Medicine: the Treatment of Disease with Traditional Chinese Medicine. Macarthur, Sydney: University of Western Sydney; 2002.
    1. Peng B. Fang X, and Wang Y(Ed): Traditional Chinese Internal Medicine. 2. Beijing: People's Medical Publishing House; 2007.
    1. Bensky D. Chinese Herbal Medicine: Formulas & Strategies. Washington: Eastland Press; 1990.
    1. Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology, and Applications. Amsterdam: Harwood Academic; 1998.
    1. Li X, Wei W. Chinese Materia Medica: Combinations and Applications. Donica: St. Albans; 2002.
    1. Cheng CW, Bian ZX, Wu TX. Systematic review of Chinese herbal medicine for functional constipation. World J Gastroenterol. 2009;15:4886–4895. doi: 10.3748/wjg.15.4886.
    1. Lai TS. Clinical Handbook of Chinese Herbal Formulae. Beijing: People's Medical Publishing House; 1996.
    1. Cheng CW, Bian ZX, Zhu LX, Wu JC, Sung JJ. Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation. Am J Gastroenterol. 2011;106:120–129. doi: 10.1038/ajg.2010.305.
    1. Kositchaiwat S, Suwanthanmma W, Suvikapakornkul R, Tiewthanom V, Rerkpatanakit P, Tinkornrusmee C. Comparative study of two bowel preparation regimens for colonoscopy: senna tablets vs sodium phosphate solution. World J Gastroenterol. 2006;12:5536–5539.
    1. Alexande FC, Nicole SC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2007;60:209–218.
    1. Central Co-ordinating Committee (Medicine) Handbook of Internal Medicine. Hong Kong: Hong Kong Hospital Authority; 2008.
    1. Moher D, Schulz KF, Altman DG. CONSORT. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol. 2001;1:2.
    1. Lembo AJ, Kurtz CB, Macdouqall JE, Lavins BJ, Currie MG, Fitch DA, Jeqlinski BI, Johnston JM. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010;138:886–895. doi: 10.1053/j.gastro.2009.12.050.
    1. Johnston JM, Kurtz CB, Drossman DA, Lembo AJ, Jeqlinski BI, MacDouqll JE, Antonelli SM, Currie MG. Pilot study on the effect of linaclotide in patients with chronic constipation. Am J Gastroenterol. 2009;104:125–132. doi: 10.1038/ajg.2008.59.
    1. Amato A, Radaelli F, Paggi S, Terruzzi V. Half doses of PEG-ES and senna vs. high-dose senna for bowel cleansing before colonoscopy: a randomized, investigator-blinded trial. Am J Gastroenterol. 2010;105:675–681. doi: 10.1038/ajg.2009.598.
    1. Mueller-Lissner S, Kamm MA, Wald A, Hinkel U, Koehler U, Richter E, Bubeck J. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol. 2010;105:897–903. doi: 10.1038/ajg.2010.41.
    1. Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. 2010. Beijing: People’s Medical Publishing House; 2010.
    1. Parkman HP, Rao SS, Reynolds JC, Schiller LR, Wald A, Miner PB, Lembo AJ, Gordon JM, Drossman DA, Waltzman L, Stambler N, Cedarbaum JM. Neurotrophin-3 improves functional constipation. Am J Gastroenterol. 2003;98:1338–1347. doi: 10.1111/j.1572-0241.2003.t01-1-07477.x.
    1. Chan AO, Hui MW, Leung G, Hu WH, Lam SK, Wong BC. Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single centre. Aliment Pharmacol Ther. 2007;25:463–469.
    1. Kamm MA, Müller-Lissner S, Talley NJ, Tack J, Boeckxstaens G, Minushkin ON, Kalinin A, Dzieniszewski J, Haeck P, Fordham F, Hugot-Cournez S, Nault B. Tegaserod for the treatment of chronic constipation: a randomized, double-blind, placebo-controlled multinational study. Am J Gastroenterol. 2005;100:362–372. doi: 10.1111/j.1572-0241.2005.40749.x.
    1. Konsyl Pharmaceuticals. Sitzmarks diagnostic test. [ ]
    1. Park JM, Choi MG, Choi H, Cho YK, Oh JH, Lee IS, Kim SW, Choi KY, Chung IS. Measurement of colonic transit using a delayed-release capsule containing radio-opaque markers. Scand J Gastroenterol. 2008;43:545–550. doi: 10.1080/00365520701850204.
    1. Wexner DS, Duthie GS. Constipation: Etiology, Evaluation, and Management. London: Springer; 2006.
    1. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J. C Bombardier: Recommendations for reporting randomized controlled trials of herbal interventions: explanation and elaboration. J Clin Epidemiol. 2006;59:1134–1149. doi: 10.1016/j.jclinepi.2005.12.020.
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher DSPIRIT. Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med. 2013;2013:200–207.
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586.

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