中医辨证治疗功能性消化不良的疗效评价以及对核素胃排空影响的多中心、随机、双盲、安慰剂对照研究
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摘要
背景
功能性消化不良(Functional Dyspepsia FD)是一组来源于胃、十二指肠的消化不良症状,并且缺乏可以解释上述症状的器质性病变和代谢性异常。FD的发病机制复杂多元化,缺乏同质性,是一组异质性综合征。临床上尚缺乏高效、有针对性的治疗措施。中医药的辨证论治对该病的治疗有较好的疗效。目前对于病理机制复杂的异质性综合征提倡个体化治疗和综合治疗,中医规范化辨证论治对于治疗FD具有非常重要的意义。
目的
本研究旨在探讨规范化的中医辨证论治方案治疗FD的疗效,以及不同中医证型FD患者胃排空特点和中医辨证论治对核素胃排空功能的影响。
材料及方法
本研究采用随机、双盲、多中心、安慰剂对照临床研究,共收集了2009年7月-2012年8月就诊于中日友好医院、北京中医药大学东直门医院、北京协和医院确诊为FD的271例患者,其中男性93例,女性180例,男女比例为1：1.94,男性平均年龄40.1±12.3岁,女性42.0±12.5岁。根据中医辨证将FD患者分为湿热壅滞证、脾虚气滞证、肝胃气滞证和肝胃郁热证四组,随机分为治疗组与对照组,分别给予相应中药配方颗粒及中药模拟剂治疗,治疗前对患者进行健康教育、饮食指导、心理疏导。(1)症状积分疗效评价：分别于治疗前、治疗第14天、第28天、治疗后第3月、第6月评价患者的中、西医症状积分进行评价。(2)核素胃排空疗效评价：分别于治疗前、治疗第28天进行核素胃排空检查。(3)治疗前及第28天进行安全性指标评价。采用SPSS11.5统计软件进行分析,分析人群包括意向治疗人群、符合方案人群。疗效分析按符合方案人群,安全性分析按意向治疗人群。
结果
1症状积分比较
1.1基线资料比较
湿热壅滞证男性患者比例较其他证型显著升高(P=0.000)；餐后饱胀积分以湿热壅滞证最高,肝胃郁热证最低,二者比较具显著性差异(P<0.05)；上腹痛症状积分以肝胃郁热证最高,与其他证型比较具显著性差异(P<0.05)。
1.2治疗后积分及疗效评价
(1)总体比较：
症状积分比较：治疗14天后,治疗组和对照组的中、西医症状积分、餐后饱胀积分早饱积分、上腹痛积分、上腹烧灼感积分与治疗前比较均显著下降(P<0.05)。治疗28天后,治疗组和对照组之间的中西医症状积分、早饱积分及上腹痛积分下降程度治疗组显著高于对照组(P<0.05)；治疗后3月,两组之间的西医积分和早饱积分的下降程度存在显著性差异,治疗组的下降程度高于对照组(P<0.05)；治疗后6月,治疗组的中医症状积分及上腹痛积分的下降程度显著高于对照组,且存在显著性差异(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(65.1%vs55.4%)、28天(76.4%vs56.3%)、3月(73.6%vs58.9%)、6月(72.0%vs59.7%),治疗28天、治疗第3月、治疗第6月中、西医症状疗效治疗组均显著优于对照组(P<0.05)。协方差分析：14天积分疗效比较在控制基线、不同试验中心和不同证型的影响后,两组之间比较无显著性差异；28天、3月中西医积分疗效指数、早饱积分下降程度,6月中医症状疗效指数具显著性差异(P<0.05)。
(2)湿热壅滞证：
症状积分比较：治疗第14天、第28天、治疗后3月、6月治疗组、对照组与治疗前比较,中西医症状积分及餐后饱胀、早饱、上腹痛、上腹烧灼感积分均显著下降(P<0.05),积分下降程度治疗组与对照组之间均无显著性差异(P>0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(60.0%vs54.2%)、28天(72.7%vs57.1%)、3月(69.7%vs60.0%)、6月(69.7%vs77.1%),治疗组与对照组比较无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)
(3)脾虚气滞证：
症状积分比较：治疗后治疗组、对照组与治疗前比较,中西医症状积分及餐后饱胀、早饱、上腹痛、上腹烧灼感积分均显著下降(P<0.05)；治疗第28天、3月、6月中、西医症状积分治疗组较对照组显著下降(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(63.3%vs41.9%)、28天(80.0%vs41.9%)、3月(80.0%vs45.2%)、6月(76.7%vs45.2%),治疗组中、西医症状疗效的显著均高于对照组(P<0.05),利用协方差在控制基线影响和不同试验中心的影响后,两组之间仍存在显著性差异(P<0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天两组之间比较无显著性差异；28天、3月中西医疗效指数、早饱积分下降程度,6月中西医疗效指数、腹痛积分下降程度两组具显著性差异(P<0.05)
(4)肝胃气滞证：
症状积分比较：治疗后治疗组、对照组中、西医症状积分及餐后饱胀、早饱、上腹痛症状积分较治疗前均显著下降(P<0.05)；治疗第14天、28天、3月各症状积分下降程度治疗组与对照组比较无显著性差异,治疗第6月上腹痛积分下降程度治疗组与对照组有显著性差异(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(59.4%vs57.4%)、28天(71.9%vs54.5%)、3月(62.5%vs54.5%)、6月(68.8%vs51.5%),治疗组与对照组无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)
(5)肝胃郁热证：
症状积分比较：治疗后治疗组、对照组与治疗前比较,中、西医症状积分及餐后饱胀、早饱、上腹痛症状积分均显著下降(P<0.05)；治疗第14天、28天、3月、6月治疗组与对照组积分下降程度无显著性差异(P>0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(77.4%vs67.7%)、28天(86.7%vs76.7%)、3月(83.3%vs80.0%)、6月(80.0%vs86.7%),治疗组与对照组比较均无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)。
2核素胃排空比较
2.1基线资料比较
(1)84例患者中,胃排空延迟者占46例(54.8%)和胃排空正常38例(45.2%)。(2)不同证型胃半排空时间具有显著性差异(P<0.05),肝胃气滞型为最长(140.7±55.3)min、其次为脾虚气滞型(134.3±64.6)min、肝胃郁热证(118.7±27.4)min,湿热壅滞型为最短(100.8±26.7)min；
(3)不同证型胃排空速率具有显著差异,湿热壅滞型最高(0.53±0.12),与其他证型比较具显著差异(P<0.05)；
(4)不同证型2小时存留率具有显著差异(P<0.05),肝胃气滞证(51.0%±14.7%)肝胃郁热证(46.9%±11.6%)与湿热壅滞证(37.2%±12.8%)比较具有显著性差异
(P<0.05)。
2.2治疗28天后核素胃排空结果比较
(1)胃半排空时间≥l1Omin：共31例,其中治疗组14例,对照组17例。治疗组治疗后排空速率和2小时存留率与治疗前比较具有显著性差异(P<0.05)；对照组治疗后2小时残留率较治疗前显著减少(P<0.05)；治疗组与对照组比较均无显著性差异(P>0.05)
(2)胃半排空时间在<11Omin：其中治疗组17例,对照组14例。治疗组、对照组治疗前后自身比较得出,治疗后胃半排空时间、胃排空率、2小时存留率与治疗前比较均无显著性差异(P>0.05)。
(3)肝胃气滞证治疗组治疗后排空率较治疗前显著上升、2小时残留率较治疗前显著下降(P<0.05)
2.3治疗前后胃排空变化与各症状积分变化的关系
胃半排空时间≥110min组胃排空率升高程度与西医积分、餐后饱胀积分下降程度呈正相关；2小时存留率减少程度与中西医积分、餐后饱胀程度下降程度呈正相关。4.安全性评价：安全性评价两组患者均无严重不良反应。
结论
1中医辨证论治治疗功能性消化不良疗效安全、确切,近期、远期均有显著疗效；香砂六君子汤合枳术丸加减治疗脾虚气滞证FD疗效确切。
2安慰剂治疗FD有一定的疗效。
3湿热壅滞证FD呈胃排空加速表现；肝胃气滞证、脾虚气滞证FD呈胃排空延迟表现。
4中医辩证治疗后胃排空延迟的FD患者胃排空功能改善。
5中医辨证治疗后胃排空功能的改善与症状改善、餐后饱胀改善相关。
Background:
Functional dyspepsia (FD) is defined by the Rome III consensus as persistent or recurrent pain or discomfort centered in the upper abdomen, without evidence of organic disease. In the past decade, our understanding of functional dyspepsia and its pathophysiology has been extended and it is now incontrovertible that the spectrum of symptoms which characterizes the disorder can be produced by numerous mechanisms. Although the cause of FD is not clear, more and more evidence showed that delayed gastric emptying and psychosocial factors were involved in FD. Successful management of functional dyspepsia remains an elusive goal for gastroenterologists because our advancing knowledge of its pathophysiology has not been paralleled by a burgeoning of appropriately targeted agents. In recent years, Traditional Chinese Medicine (TCM) showed more effective in the management of FD with medicine at the same time.
Objective:
The purpose of this study was to evaluate efficacy and safety of TCM differentiating treatment, the feature of gastric emptying in FD patients with different TCM Syndromes and the influence of TCM syndrome on radionuclide gastric emptying.
Materials and methods:
This study was a random, double-blind, multicenter, placebo-controlled clinical study.273cases of FD patients were recruited from China-Japan Friendship Hospital, Dongzhimen hospital and Peking Union Medical College Hospital on2009July to2012August. This study included93males and180females (male to female ratio:1:1.94). Mean age in male was40.1±12.3years and42±12.5years in female. According to differentiation, patients were divided into stagnation of damp-heat syndrome, spleen deficiency and qi stagnation syndrome, liver qi stagnation syndrome and stagnated heat in liver and stomach syndrome, and given corresponding traditional Chinese medicine. Evaluation of efficacy:The score of TCM and west medicine symptoms of baseline,14th day,18th day, third month,6th month was assesed. Radionuclide gastric emptying was evaluated. SPSS16.0was used to analysis intent-to-treat population, population including the per-protocol population, curative effect in the per-protocol population, safety evaluated according to the intention-to-treat population.
Results:
1Symptom scores evaluation
1.1Compared to baseline data:
All scores in the stagnation of damp-heat syndrome type in male was significantly higher than other types (P=0.000). Postprandial fullness syndrome score was significantly highest in stagnation of damp-heat syndrome and lowest in stagnated heat of liver and stomach syndrome(P<0.05); the upper abdominal pain symptoms score was highest in liver and stomach heat type compared with other types (P<0.05).
1.2Symptom scores and efficiency evaluation
(1) Compared symptom scores:TCM integrate score, Western medicine integrate score, postprandial fullness, early satiety, upper abdominal pain, epigastric burning sensation score in treatment group were significantly decreased after14th day(P<0.05). For28th day,3rd month,6th months, western medicine symptom score decreased in treatment group was higher than that of control group (P<0.05). For28th days and3rd month, early satiety score and upper abdominal pain symptom score in treatment group was decreased significantly than those of the control group (P<0.05). For6th month, abdominal pain integral in treatment group was decreased significantly than that in the control group (P<0.05). Efficiency comparison:for14th days of treatment, Western Medicine symptoms in treatment and control had no significant difference. For28th day of treatment,3rd month,6th month, clinical symptoms of western medicine in treatment group was significantly better than that in control (P<0.05). TCM symptom integrate in treatment and controls were14days (65.1%vs55.4%),28days (76.4%vs56.3%),3months (73.6%vs58.9%),6months (72.0%vs59.7%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, we found no difference of all kinds of score between treatment group and controls in14th day. Western medicine integrate and early satiety scores of28th day and third month improved significantly, and TCM integrate score of6th month decreased significantly(P<0.05).
(2) Stagnation of damp-heat syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after28days,3months,6months(P>0.05). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
(3) Spleen deficiency and Qi stagnation:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was significant difference between the two group, and TCM score, WE score were significantly after28days,3months,6months(P<0.05). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day (P>0.05). TCM integrate score, Western medicine integrate and early satiety scores of28th day and third month improved significantly, and TCM integrate score, Western medicine integrate and upper abdominal pain scores of6th month also was found decreased significantly(P<0.05).
(4) Liver qi stagnation syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after14days,28days,3months (P>0.05). But there was significant difference between the two group, and TCM score, WE score were significantly after6months(P<0.05). Effective percentage of TCM clinical symptoms between treatment group and contr ols:14days (59.4%vs57.4%),28days (71.9%vs54.5%),3months (62.5%vs54.5%),6months (68.8%vs51.5%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
(5)Stagnated heat in liver and stomach syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after28days,3months,6months(P>0.05). Effective percentage of TCM clinical symptoms between treatment group and controls:14days (77.4%vs67.7%),28days (86.7%vs76.7%),3rd month (83.3%vs80.0%),6th month (80.0%vs86.7%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
2Comparison of gastric emptying
2.1Comparison of baseline data
2.1.1There were46cases (54.8%) with delayed gastric emptying time,38cases (45.2%) with normal gastric emptying time among84cases.
2.1.2There was significant difference among different types.
(1)There was significant difference among different types in gastric half emptying time: stagnation of damp-heat type gastric half emptying time (100.8±26.7), liver qi stagnation type (140.7±55.3), spleen deficiency and qi stagnation type (134.3±64.6) and stagnation of damp-heat type (118.7±27.4).
(2) There was significant difference among different types in gastric emptying rate: stagnation of damp-heat type gastric emptying rate (0.53±0.12) was significantly faster than other types(P<0.05), and there was no significant difference between the other types (P>0.05).
(3) There was significant difference among different types in2hours retention rate: stagnation of damp-heat type (37.2±12.8%)was significant lower than liver and stomach qi stagnation (51%±14.7%). stagnation of liver and stomach heat syndrome (46.9%± 11.6%).
2.2Comparison of28days treatment in radionuclide gastric emptying:
(1) gastric half emptying time more than110min case:there were14cases in treatment group and17cases in the control group. Gastric emptying rate after treatment and2hour gasric residulal rate had significant difference in treatment group and controls (P<0.05). But it showed no significant difference between controls and treatment group (P>0.05).
(2)Gastric emptying time less than110min:there were17cases in treatment group and14cases in the control group. But it showed no significant difference between controls and treatment group (P>0.05).
(3) Liver qi stagnation syndrome after treatment the emptying rate significantly compared with those before treatment,2hours gastric residual rate significantly decreased than that before treatment (P<0.05).
2.3The relationship between Gastric emptying and symptom score changes before and after the treatment
In gastric half emptying time more than110min group.the changes of gastric emptying rate was associate with the changes of western medicine symptom score and postprandial full score.2hours retention rate reduced degree was associated with the declined degree of symptom score and postprandial full score.
3Safety evaluation:There were no serious adverse in both groups.
Conclusions:
1TCM differentiating treatment on patients with functional dyspepsia was effective and safe. Treatment of spleen deficiency and qi stagnation syndrome was more effective.
2. The placebo have certain efficacy to treat FD patient.
3Stagnation of damp-heat type appears accelerated gastric emptying function, Spleen deficiency and qi stagnation type and Liver and stomach qi stagnation type appears delayed gastric emptying function.
4.TCM differentiating treatment could improve the gastric emptying function of FD patients with delayed gastric emptying.
5.Through TCM differentiating treatment, the Improvement degree of function of gastric emptying was associated with the declined degree of symptom score and postprandial fullness score.
功能性消化不良(Functional Dyspepsia FD)是一组来源于胃、十二指肠的消化不良症状,并且缺乏可以解释上述症状的器质性病变和代谢性异常。FD的发病机制复杂多元化,缺乏同质性,是一组异质性综合征。临床上尚缺乏高效、有针对性的治疗措施。中医药的辨证论治对该病的治疗有较好的疗效。目前对于病理机制复杂的异质性综合征提倡个体化治疗和综合治疗,中医规范化辨证论治对于治疗FD具有非常重要的意义。
目的
本研究旨在探讨规范化的中医辨证论治方案治疗FD的疗效,以及不同中医证型FD患者胃排空特点和中医辨证论治对核素胃排空功能的影响。
材料及方法
本研究采用随机、双盲、多中心、安慰剂对照临床研究,共收集了2009年7月-2012年8月就诊于中日友好医院、北京中医药大学东直门医院、北京协和医院确诊为FD的271例患者,其中男性93例,女性180例,男女比例为1：1.94,男性平均年龄40.1±12.3岁,女性42.0±12.5岁。根据中医辨证将FD患者分为湿热壅滞证、脾虚气滞证、肝胃气滞证和肝胃郁热证四组,随机分为治疗组与对照组,分别给予相应中药配方颗粒及中药模拟剂治疗,治疗前对患者进行健康教育、饮食指导、心理疏导。(1)症状积分疗效评价：分别于治疗前、治疗第14天、第28天、治疗后第3月、第6月评价患者的中、西医症状积分进行评价。(2)核素胃排空疗效评价：分别于治疗前、治疗第28天进行核素胃排空检查。(3)治疗前及第28天进行安全性指标评价。采用SPSS11.5统计软件进行分析,分析人群包括意向治疗人群、符合方案人群。疗效分析按符合方案人群,安全性分析按意向治疗人群。
结果
1症状积分比较
1.1基线资料比较
湿热壅滞证男性患者比例较其他证型显著升高(P=0.000)；餐后饱胀积分以湿热壅滞证最高,肝胃郁热证最低,二者比较具显著性差异(P<0.05)；上腹痛症状积分以肝胃郁热证最高,与其他证型比较具显著性差异(P<0.05)。
1.2治疗后积分及疗效评价
(1)总体比较：
症状积分比较：治疗14天后,治疗组和对照组的中、西医症状积分、餐后饱胀积分早饱积分、上腹痛积分、上腹烧灼感积分与治疗前比较均显著下降(P<0.05)。治疗28天后,治疗组和对照组之间的中西医症状积分、早饱积分及上腹痛积分下降程度治疗组显著高于对照组(P<0.05)；治疗后3月,两组之间的西医积分和早饱积分的下降程度存在显著性差异,治疗组的下降程度高于对照组(P<0.05)；治疗后6月,治疗组的中医症状积分及上腹痛积分的下降程度显著高于对照组,且存在显著性差异(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(65.1%vs55.4%)、28天(76.4%vs56.3%)、3月(73.6%vs58.9%)、6月(72.0%vs59.7%),治疗28天、治疗第3月、治疗第6月中、西医症状疗效治疗组均显著优于对照组(P<0.05)。协方差分析：14天积分疗效比较在控制基线、不同试验中心和不同证型的影响后,两组之间比较无显著性差异；28天、3月中西医积分疗效指数、早饱积分下降程度,6月中医症状疗效指数具显著性差异(P<0.05)。
(2)湿热壅滞证：
症状积分比较：治疗第14天、第28天、治疗后3月、6月治疗组、对照组与治疗前比较,中西医症状积分及餐后饱胀、早饱、上腹痛、上腹烧灼感积分均显著下降(P<0.05),积分下降程度治疗组与对照组之间均无显著性差异(P>0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(60.0%vs54.2%)、28天(72.7%vs57.1%)、3月(69.7%vs60.0%)、6月(69.7%vs77.1%),治疗组与对照组比较无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)
(3)脾虚气滞证：
症状积分比较：治疗后治疗组、对照组与治疗前比较,中西医症状积分及餐后饱胀、早饱、上腹痛、上腹烧灼感积分均显著下降(P<0.05)；治疗第28天、3月、6月中、西医症状积分治疗组较对照组显著下降(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(63.3%vs41.9%)、28天(80.0%vs41.9%)、3月(80.0%vs45.2%)、6月(76.7%vs45.2%),治疗组中、西医症状疗效的显著均高于对照组(P<0.05),利用协方差在控制基线影响和不同试验中心的影响后,两组之间仍存在显著性差异(P<0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天两组之间比较无显著性差异；28天、3月中西医疗效指数、早饱积分下降程度,6月中西医疗效指数、腹痛积分下降程度两组具显著性差异(P<0.05)
(4)肝胃气滞证：
症状积分比较：治疗后治疗组、对照组中、西医症状积分及餐后饱胀、早饱、上腹痛症状积分较治疗前均显著下降(P<0.05)；治疗第14天、28天、3月各症状积分下降程度治疗组与对照组比较无显著性差异,治疗第6月上腹痛积分下降程度治疗组与对照组有显著性差异(P<0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(59.4%vs57.4%)、28天(71.9%vs54.5%)、3月(62.5%vs54.5%)、6月(68.8%vs51.5%),治疗组与对照组无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)
(5)肝胃郁热证：
症状积分比较：治疗后治疗组、对照组与治疗前比较,中、西医症状积分及餐后饱胀、早饱、上腹痛症状积分均显著下降(P<0.05)；治疗第14天、28天、3月、6月治疗组与对照组积分下降程度无显著性差异(P>0.05)。有效率比较：治疗组与对照组中医症状有效率分别为14天(77.4%vs67.7%)、28天(86.7%vs76.7%)、3月(83.3%vs80.0%)、6月(80.0%vs86.7%),治疗组与对照组比较均无显著性差异(P>0.05)。协方差分析：在控制基线、不同试验中心和不同证型的影响后,14天、28天、3月、6月两组之间比较均无显著性差异(P>0.05)。
2核素胃排空比较
2.1基线资料比较
(1)84例患者中,胃排空延迟者占46例(54.8%)和胃排空正常38例(45.2%)。(2)不同证型胃半排空时间具有显著性差异(P<0.05),肝胃气滞型为最长(140.7±55.3)min、其次为脾虚气滞型(134.3±64.6)min、肝胃郁热证(118.7±27.4)min,湿热壅滞型为最短(100.8±26.7)min；
(3)不同证型胃排空速率具有显著差异,湿热壅滞型最高(0.53±0.12),与其他证型比较具显著差异(P<0.05)；
(4)不同证型2小时存留率具有显著差异(P<0.05),肝胃气滞证(51.0%±14.7%)肝胃郁热证(46.9%±11.6%)与湿热壅滞证(37.2%±12.8%)比较具有显著性差异
(P<0.05)。
2.2治疗28天后核素胃排空结果比较
(1)胃半排空时间≥l1Omin：共31例,其中治疗组14例,对照组17例。治疗组治疗后排空速率和2小时存留率与治疗前比较具有显著性差异(P<0.05)；对照组治疗后2小时残留率较治疗前显著减少(P<0.05)；治疗组与对照组比较均无显著性差异(P>0.05)
(2)胃半排空时间在<11Omin：其中治疗组17例,对照组14例。治疗组、对照组治疗前后自身比较得出,治疗后胃半排空时间、胃排空率、2小时存留率与治疗前比较均无显著性差异(P>0.05)。
(3)肝胃气滞证治疗组治疗后排空率较治疗前显著上升、2小时残留率较治疗前显著下降(P<0.05)
2.3治疗前后胃排空变化与各症状积分变化的关系
胃半排空时间≥110min组胃排空率升高程度与西医积分、餐后饱胀积分下降程度呈正相关；2小时存留率减少程度与中西医积分、餐后饱胀程度下降程度呈正相关。4.安全性评价：安全性评价两组患者均无严重不良反应。
结论
1中医辨证论治治疗功能性消化不良疗效安全、确切,近期、远期均有显著疗效；香砂六君子汤合枳术丸加减治疗脾虚气滞证FD疗效确切。
2安慰剂治疗FD有一定的疗效。
3湿热壅滞证FD呈胃排空加速表现；肝胃气滞证、脾虚气滞证FD呈胃排空延迟表现。
4中医辩证治疗后胃排空延迟的FD患者胃排空功能改善。
5中医辨证治疗后胃排空功能的改善与症状改善、餐后饱胀改善相关。
Background:
Functional dyspepsia (FD) is defined by the Rome III consensus as persistent or recurrent pain or discomfort centered in the upper abdomen, without evidence of organic disease. In the past decade, our understanding of functional dyspepsia and its pathophysiology has been extended and it is now incontrovertible that the spectrum of symptoms which characterizes the disorder can be produced by numerous mechanisms. Although the cause of FD is not clear, more and more evidence showed that delayed gastric emptying and psychosocial factors were involved in FD. Successful management of functional dyspepsia remains an elusive goal for gastroenterologists because our advancing knowledge of its pathophysiology has not been paralleled by a burgeoning of appropriately targeted agents. In recent years, Traditional Chinese Medicine (TCM) showed more effective in the management of FD with medicine at the same time.
Objective:
The purpose of this study was to evaluate efficacy and safety of TCM differentiating treatment, the feature of gastric emptying in FD patients with different TCM Syndromes and the influence of TCM syndrome on radionuclide gastric emptying.
Materials and methods:
This study was a random, double-blind, multicenter, placebo-controlled clinical study.273cases of FD patients were recruited from China-Japan Friendship Hospital, Dongzhimen hospital and Peking Union Medical College Hospital on2009July to2012August. This study included93males and180females (male to female ratio:1:1.94). Mean age in male was40.1±12.3years and42±12.5years in female. According to differentiation, patients were divided into stagnation of damp-heat syndrome, spleen deficiency and qi stagnation syndrome, liver qi stagnation syndrome and stagnated heat in liver and stomach syndrome, and given corresponding traditional Chinese medicine. Evaluation of efficacy:The score of TCM and west medicine symptoms of baseline,14th day,18th day, third month,6th month was assesed. Radionuclide gastric emptying was evaluated. SPSS16.0was used to analysis intent-to-treat population, population including the per-protocol population, curative effect in the per-protocol population, safety evaluated according to the intention-to-treat population.
Results:
1Symptom scores evaluation
1.1Compared to baseline data:
All scores in the stagnation of damp-heat syndrome type in male was significantly higher than other types (P=0.000). Postprandial fullness syndrome score was significantly highest in stagnation of damp-heat syndrome and lowest in stagnated heat of liver and stomach syndrome(P<0.05); the upper abdominal pain symptoms score was highest in liver and stomach heat type compared with other types (P<0.05).
1.2Symptom scores and efficiency evaluation
(1) Compared symptom scores:TCM integrate score, Western medicine integrate score, postprandial fullness, early satiety, upper abdominal pain, epigastric burning sensation score in treatment group were significantly decreased after14th day(P<0.05). For28th day,3rd month,6th months, western medicine symptom score decreased in treatment group was higher than that of control group (P<0.05). For28th days and3rd month, early satiety score and upper abdominal pain symptom score in treatment group was decreased significantly than those of the control group (P<0.05). For6th month, abdominal pain integral in treatment group was decreased significantly than that in the control group (P<0.05). Efficiency comparison:for14th days of treatment, Western Medicine symptoms in treatment and control had no significant difference. For28th day of treatment,3rd month,6th month, clinical symptoms of western medicine in treatment group was significantly better than that in control (P<0.05). TCM symptom integrate in treatment and controls were14days (65.1%vs55.4%),28days (76.4%vs56.3%),3months (73.6%vs58.9%),6months (72.0%vs59.7%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, we found no difference of all kinds of score between treatment group and controls in14th day. Western medicine integrate and early satiety scores of28th day and third month improved significantly, and TCM integrate score of6th month decreased significantly(P<0.05).
(2) Stagnation of damp-heat syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after28days,3months,6months(P>0.05). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
(3) Spleen deficiency and Qi stagnation:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was significant difference between the two group, and TCM score, WE score were significantly after28days,3months,6months(P<0.05). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day (P>0.05). TCM integrate score, Western medicine integrate and early satiety scores of28th day and third month improved significantly, and TCM integrate score, Western medicine integrate and upper abdominal pain scores of6th month also was found decreased significantly(P<0.05).
(4) Liver qi stagnation syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after14days,28days,3months (P>0.05). But there was significant difference between the two group, and TCM score, WE score were significantly after6months(P<0.05). Effective percentage of TCM clinical symptoms between treatment group and contr ols:14days (59.4%vs57.4%),28days (71.9%vs54.5%),3months (62.5%vs54.5%),6months (68.8%vs51.5%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
(5)Stagnated heat in liver and stomach syndrome:TCM score, WE score, postprandial fullness score, early satiety score, epigastric pain score, epigastric burning sensation scores were significantly decreased in treatment group after14days treatment(P<0.05). There was no significant difference between the two group and also found after28days,3months,6months(P>0.05). Effective percentage of TCM clinical symptoms between treatment group and controls:14days (77.4%vs67.7%),28days (86.7%vs76.7%),3rd month (83.3%vs80.0%),6th month (80.0%vs86.7%). After adjusting the baseline, different clinical trial centers and different symptoms by covariance analysis, no difference was found for all kind of scores in14th day,28th day,3rd month and6th month(P>0.05).
2Comparison of gastric emptying
2.1Comparison of baseline data
2.1.1There were46cases (54.8%) with delayed gastric emptying time,38cases (45.2%) with normal gastric emptying time among84cases.
2.1.2There was significant difference among different types.
(1)There was significant difference among different types in gastric half emptying time: stagnation of damp-heat type gastric half emptying time (100.8±26.7), liver qi stagnation type (140.7±55.3), spleen deficiency and qi stagnation type (134.3±64.6) and stagnation of damp-heat type (118.7±27.4).
(2) There was significant difference among different types in gastric emptying rate: stagnation of damp-heat type gastric emptying rate (0.53±0.12) was significantly faster than other types(P<0.05), and there was no significant difference between the other types (P>0.05).
(3) There was significant difference among different types in2hours retention rate: stagnation of damp-heat type (37.2±12.8%)was significant lower than liver and stomach qi stagnation (51%±14.7%). stagnation of liver and stomach heat syndrome (46.9%± 11.6%).
2.2Comparison of28days treatment in radionuclide gastric emptying:
(1) gastric half emptying time more than110min case:there were14cases in treatment group and17cases in the control group. Gastric emptying rate after treatment and2hour gasric residulal rate had significant difference in treatment group and controls (P<0.05). But it showed no significant difference between controls and treatment group (P>0.05).
(2)Gastric emptying time less than110min:there were17cases in treatment group and14cases in the control group. But it showed no significant difference between controls and treatment group (P>0.05).
(3) Liver qi stagnation syndrome after treatment the emptying rate significantly compared with those before treatment,2hours gastric residual rate significantly decreased than that before treatment (P<0.05).
2.3The relationship between Gastric emptying and symptom score changes before and after the treatment
In gastric half emptying time more than110min group.the changes of gastric emptying rate was associate with the changes of western medicine symptom score and postprandial full score.2hours retention rate reduced degree was associated with the declined degree of symptom score and postprandial full score.
3Safety evaluation:There were no serious adverse in both groups.
Conclusions:
1TCM differentiating treatment on patients with functional dyspepsia was effective and safe. Treatment of spleen deficiency and qi stagnation syndrome was more effective.
2. The placebo have certain efficacy to treat FD patient.
3Stagnation of damp-heat type appears accelerated gastric emptying function, Spleen deficiency and qi stagnation type and Liver and stomach qi stagnation type appears delayed gastric emptying function.
4.TCM differentiating treatment could improve the gastric emptying function of FD patients with delayed gastric emptying.
5.Through TCM differentiating treatment, the Improvement degree of function of gastric emptying was associated with the declined degree of symptom score and postprandial fullness score.
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