Treating IBS-D with TCM. Jiang Lin, MD.&PhD. Gastroenterology Dept. of Shuguang Hospital, Shanghai University of TCM

Transcription

1 Treating IBS-D with TCM Jiang Lin, MD.&PhD. Gastroenterology Dept. of Shuguang Hospital, Shanghai University of TCM

2 Content Does TCM work in IBS-D treatment? How does TCM work in IBS-D treatment? How to use TCM to treat IBS-D?

3 Does TCM work in IBS-D treatment?

4 Co-Editor-in-Chief, American Journal of Gastroenterology first clinical trial in TCM that fully adheres to the protocol of EBM

5 Design of the Clinical Trial randomized, double blinded, placebo controlled subjectives IBS-D patients between ages of 18-75yrs intervention placebo, standard CHM or individualized CHM 16-week intervention and 14-week follow-up measurement instruments bowel symptoms scale of IBS (BSS) evaluated at week 0, 16 and 30

6 Ingredients of Standard CHM

7 Population Characteristics and BSS before and after Treatment

8 Tongxiening Granule in the treatment of IBS-D (Liver Qi Attacking Spleen): A Prospective, Randomized, Placebo Controlled, Double Blind Clinical Trial Dept. of Integrated Chinese & Western Medicine, West China Hospital, Sichuan University Chinese Journal of Evidence Based Medicine, 2006;6(2):84-89

9 Design of the Clinical Trial randomized, double blinded, placebo controlled subjectives IBS-D patients with TCM diagnosis of liver qi attacking spleen between ages of 18-65yrs intervention placebo or Tongxiening Granule 3-week intervention measurement instruments visual analog scales of abdominal pain and diarrhea TCM syndrome scale rating before and after treatment

10 Ingredients of Tongxiening Granule Chinese name pharmaceutical name weights(%) Baishao radix paeoniae alba Baizhu Qingpi Xiebai rhizoma atractylodis macrocephalae pericarpium citri reticulatae viride bulbus allii macrostemoni

11 abdominal pain group n cure % marked Efficacy comparison between TXN & placebo % effective % ineffective ITT TXN 29 9(31.0) 9(31.0) 6(20.7) 5(17.2) Placebo 28 2(7.1) 4(14.3) 5(17.9) 17(60.7) PP TXN 26 15(57.7) 3(11.5) 6(23.1) 2(7.7) diarrhea Placebo 25 4(16.0) 2(8.0) 5(20.0) 14(56.0) ITT TXN 29 12(41.4) 6(20.7) 7(24.1) 4(13.8) Placebo 28 5(17.9) 2(7.7) 5(17.9) 16(57.1) PP TXN 26 12(46.2) 6(23.7) 7(26.9) 1(3.9) TCM syndrome scale Placebo 25 5(20.0) 2(8.0) 5(20.0) 13(52.0) ITT TXN 29 8(27.6) 11(37.9) 5(17.2) 5(17.2) Placebo 28 1(3.6) 5(17.9) 6(21.4) 16(57.1) % p

12 Changjitai Granule in the treatment of IBS-D : A Randomized, Placebo Controlled, Double Blind Clinical Trial Department of gastroenterology, Shuguang Hospital, Shanghai University of TCM Shanghai Journal of TCM, 2010; 44(12): 33-37

13 Design of the Clinical Trial randomized, double blinded, placebo controlled subjectives IBS-D patients with TCM diagnosis of liver qi attacking spleen between ages of 18-60yrs intervention placebo or Changjitai Granule (CJT) 4-week intervention measurement instruments IBS Bowel Symptoms Scale (IBS-BSS), primary efficacy index IBS Defication Status Questionaire (IBS-DSQ), secondary efficacy index rating before and after treatment

14 Ingredients of Changjitai Granule Chinese name Baizhu Baishao Chenpi Fangfen Gancao Wumei Pharmceutical name rhizoma atractylodis macrocephalae radix paeoniae alba pericarpium citri reticulatae radix sileris radix liquiritiae fructus mume

15 Comparison of IBS-BSS(I) group pain severity pain days bloating satisfaction of defecation interfere with life total score CJT before treatment (22.21) (29.12) (25.58) (12.41) (20.14) (67.03) after 11.23*# 13.33*# 11.33* 40.46*# 35.00*# *# treatment (15.16) (21.87) (12.68) (19.98) (20.29) (69.85) placebo before treatment (22.81) (34.25) (26.05) (9.96) (19.76) (53.89) after 24.13* 21.18* * 53.62* * treatment (15.71) (20.57) (24.65) (23.01) (23.54) (78.65) *, intragroup comparison, p<0.05; #, intergroup comparison, p<0.05

16 Comparison of IBS-BSS(II) group n analysis set marked effective effective ineffective total effective % p CJT FAS Placebo CJT PP Placebo

17 Comparison of IBS-DSQ(I) group defecation frequency days of defecating with urgency CJT before treatment 3.03 (1.62) 6.08 (3.64) after treatment 1.60* (1.15) 1.53*# (2.29) placebo before treatment 2.55 (1.45) 6.00 (3.80) after treatment 1.83* (1.11) 3.12* (2.89) *, intragroup comparison, p<0.05; #, intergroup comparison, p<0.05

18 Comparison of IBS-DSQ(II) group n analysis set marked effective effective ineffective total effective % p CJT FAS Placebo CJT PP Placebo

19 How does TCM work in IBS-D treatment?

20 Reducing Visceral Hypersensitivity group(n) 30ml 60ml 90ml 120ml HC(10) 0.67(0.57) 1.68(1.18) 2.09(1.18) 3.08(1.25) CJT(14) Placebo(10) before treatment after treatment before treatment 0.54(0.42) 1.48(0.83) 4.75(1.68)* 6.86(1.86)* 0.44(0.23) 1.36(0.96) 2.89(2.04)# 4.32(2.82)# 0.42(0.15) 1.41(0.71) 4.28(1.05)* 6.06(2.16)* after treatment *, compared to HC, p<0.05; #, compare to before treatment, p<0.05 J Shen, et al. CJITWM, 2005;25(11): (0.16) 1.28(0.66) 3.84(1.14)* 6.45(1.54)*

21 Comparison of fmri alterations of encephalic funcitonal area CJT group befeore treatment after treatment Placebo group before treatment after treatment J Shen, et al. CJITWM, 2005;25(11):

22 Reducing 5-HT content in visceral hypersensitivity model rats intestinal mucosa group jejunum (ng/ml) ileum (ng/ml) proximal colon (ng/ml) distal colon (ng/ml) NC ± ± ± ±41.50 MC ±51.84 * ±20.19 * ±49.04 * ±50.43 * TXYF ±32.35 *# ±31.19 *# ±30.90 *# ±31.51 *# *, compared to NC, p<0.05; #, compared to MC, p<0.05

23 Increasing SERT Expression in Intestinal Mucosa group jejunum (ng/ml) ileum (ng/ml) proximal colon (ng/ml) distal colon (ng/ml) NC 0.94± ± ± ±0.30 MC 0.40±0.24* 0.35±0.21* 0.31±0.15* 0.45±0.15* TXYF 0.67±0.24*# 0.81±0.30*# 0.59±0.20*# 0.78±0.28*# *, compared to NC, p<0.05; #, compared to MC, p<0.05

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25 VGSCNav1.8 & NGF VGSC is a transmembrane glycoprotein in neuron and closely related to the generation and conduction of action potentials VGSC plays key role in visceral hypersensitivity mice with visceral hypersensitivity expressing more VGSC on dorsal root ganglia VGSC knock-out mice having little pain when stimulated by colon dilation VGSC & NGF receptor TrkA express simutaneously in neuron over-expression NGF transgenic mice over expressed VGSC NGF increasing sodium ion inflow through VGSC VGSC & NGF over expressed in model of visceral hypersensitivity

26 Comparison of Nav1.8 & NGF group(n) Nav1.8 NGF(pg/ml) NC(10) 2.89± ±69.73 MC(10) 7.22±4.18* ±82.96* Low dosage of CJT 6.45±3.51* ±100.41* High dosage of CJT 2.70±2.92# ±83.17# *, compared to NC, p<0.05; #, compared to MC, p<0.05

27 Visceral Hypersensitivity intestinal mucosal 5-HT intestinal mucosal SERT DRG VGSC Nav1.8 intestinal mucosal NGF

28 How to use TCM to treat IBS-D?

29 TCM subtypes of IBS-D 2010 Consensus on TCM diagnosis and treatment in IBS Spleen deficiency & dampness detention Liver Qi stagnation & spleen deficiency Yang deficiency of spleen & kidney Heat dampness of Spleen & stomach

30 Spleen deficiency & dampness detention Diagnosis primary symptoms loose stool or diarrhea mild abdominal pain secondary symptoms induced or worsen by tiredness or getting cold fatigue pale tongue with teeth mark, white greesy tongue fur weak pulse 2 primary symptoms plus at least 2 secondary symtoms Formula Shen Ling Bai Zhu San

31 Liver Qi stagnation & spleen deficiency Diagnosis primary symptoms diarrhea following abdominal pain and pain is relieved right after bowel movement, attacks usually related to mood irritability and impetousity, sighing frequently secondary symptoms feeling fullness in hypochondrium poor appetite and nausea swollen and pale tongue with teeth mark thin and tense pulse 2 primary symptoms plus at least 2 secondary symtoms Formula Tong Xie Yao Fang

32 Yang deficiency of spleen & kidney Diagnosis primary symptoms abdominal pain and diarrhea attacks when getting up abdominal pain is relieved by heating intorelance of cold, cold limbs secondary symptoms soreness of waist and weak legs poor appetite swollen and pale tongue with white and slippery tongue fur thin and deep pulse 2 primary symptoms plus at least 2 secondary symtoms Formula Fu Zi Li Zhong Tang and Si Shen Wan

33 Heat Dampness of Spleen and Stomach Diagnosis primary symptoms abdominal pain and diarrhea urgent stool passage or incomplete evacuation burning sensation in anus secondary symptoms chest tightness, thirsty mouth bitterness red tongue with yellow and greesy tongue fur slippery and fast pulse 2 primary symptoms plus at least 2 secondary symtoms Formula Ge Gen Qin Lian Tang

34 Comparison of the Proportion of TCM subtypes between South & North TCM subtypes proportion(%) South North SDDD LSSD YDSK HDSS 40 proportion(%)

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36 Tong Xie Yao Fang Indications Abdominal pain followed by diarrhea immediately Abdominal pain relieved by diarrhea

37 Baizhu (9) Ingredients of TXYF Rhizoma Atractylodis Macrocephalae Baishao (6) Radix Paeoniae Alba Chenpi (4.5) Pericarpium Citri Reticulatae Fangfeng (3) Radix Saposhnikoviae

38 Tailoring Treatment Spleen Deficiency Fatigue, emaciated, poor appetite, loose stool or diarrhea frequently Shen Lin Bai Zhu San Dangshen (Radix Codonopsis), Huangqi (Radix Astragali), Shanyao (Dioscorea Opposita), Baibiandou (semen dolichoris), Lianzi (Semen Nelumbinis), Qianshi (Semen Euryales)

39 Tailoring Treatment Dampness Detention Thick tongue fur Huo Xiang Zheng Qi San Yiyiren (Semen Coicis), Sharen (fructus amomi), Huoxiang (Agastache rugosa), Peilan (Herba Eupatorii), Fuling (Poria cocos)

40 Tailoring Treatment Heat Dampness Yellowish tongue fur, red tongue, bitterness, bad breath, burning sensation in anus Ge Gen Qin Lian Tang Huangqin (Scutellaria baicalensis), Huanglian (Coptis chinensis), Huangbai (Cortex Phellodendri)

41 Tailoring Treatment Yang Deficiency of spleen & kidney Intolerance of cold, cold limbs, feeling cold in abdomen, pain or discomfortableness induced by cold Fu Zi Li Zhong Tang or Si Shen Wan Fuzi (radix aconiti carmichaeli), Paojiang (baked jinger), Buguzhi (Fructus Psoraleae), Roudoukou (Semen Myristicae), Wuzhuyu ( Evodia rutaecarpa),yizhiren (semen amomi amari)

42 Tailoring Treatment Sever abdominal pain Yanhusuo (Rhizoma Corydalis), Xiangfu (Rhizoma Cyperi), Chuanxiong (Ligusticum wallichii) Severe diarrhea Wuweizi (Schisandra chinensis), Shiliupi (pericarpium granati), Hezi (Fructus Chebulae), Liushenqu (Medicated Leaven Massa Medicata Fermentata)

43 Summary CHM may be effective in IBS-D treatment, still requires large scale RCT trials to prove Liver Qi stagnation & spleen deficiency is the core TCM pathogenesis of IBS-D Tong Xie Yao Fang is the essential formula to treat IBS-D Tailored treatment based on TCM theory maybe the optimal approach in IBS-D treatment

44 Thank You For Your Attention