陳明豐 義大醫院

胃食道逆流疾病 (Gastro-esophageal reflux disease;GERD)是國人常見的上消化道疾病，其罹患率逐年增加，約佔人口的10-20%。GERD病患者經常有上腹部燒灼感、胸悶或喉痛等症狀，嚴重影響其生活品質。目前GERD的治療以質子幫浦抑制劑(proton-pump inhibitor；PPI)為主，其治療的成功率約為80-90%，但在停藥半年到一年之間，疾病復發率高達40-80%。 因此，有必要尋求安全的治療藥物，以預防疾病的復發。香砂六君子湯是常用的中藥方劑之一，傳統中醫用於脾氣虛及胃氣虛的治療。本研究的目的乃觀察香砂六君子湯是否具有加強PPI的療效果，並預防GERD復發的效果。 我們原預定招募80名臨床上具GERD症狀，且經胃鏡證實有逆流性食道炎(reflux esophagitis)，依洛杉磯分類嚴重度屬於A或B級的患者進入臨床試驗。他們在簽署受試同意書後，將被隨機分成兩組。一組(治療組)將每日一次口服西藥Rabeprazole(PPI的一種)20mg合併濃縮科學中藥粉末香砂六君子湯每日2次，一次3.5公克；另外一組(對照組)則每日一次口服西藥Rabeprazole 20mg合併安慰劑(含1/20濃度之香砂六君子湯的澱粉)每日2次，一次3.5公克。治療期共16週，我們將以症狀量表每4週一次，評估受試者症狀的變化。治療16週後，將進入第二階段(復發觀察期)，所有受試者將服用治酸劑Toppal(每日3次，一次一顆)取代rabeprazole。復發觀察期共24週。我們將每8週一次，以症狀量表評估受試者的症狀，直至其症狀出現或以胃鏡證實逆流性食道炎復發為止。我們將以unpaired Student’s t-test，分析比較兩組治療期間症狀指數的差異及復發觀察期之復發率，並比較男女性別在療效上的差異。 自101年4月1日至101年11月30日，我們已篩選了134位臨床上具胃食道逆流症狀且胃鏡檢查呈現食道發炎(A及B級)的患者，其中有123位患者加入臨床試驗。他們當中有53位(43.1%)已完成16週的治療，有31位(25.2%)尚在服藥中，有39位(31.7%)受試者退出試驗，預定將有60-70位受試者將進入第二期(追蹤)計畫。本案迄今本案尚未出現嚴重不良反應，顯示香砂六君子湯和rabeprazole合併治療的安全性。在102年度，我們將繼續完成部份未完成治療個案之治療計畫(16週)，並完成24週的追蹤計畫。我們期待衛生署中醫藥委員會能繼續支持本臨床研究團隊，完成第二階段觀察期的臨床試驗。我們相信，此研究將有助於GERD的治療及預防，並有助於中藥中藥在臨床的應用。

關鍵詞: 香砂六君子湯、逆流性食道炎

The effects of Xiangsha-liujunzi-tang to improve symptoms and to prevent the recurrence of reflux esophagitis.

Ming-Feng Chen E-Da Hospital

Gastro-esophageal reflux disease (GERD) is a common disease of upper gastrointestinal tract in Taiwan. The prevalence of GERD in Taiwan is about 10-20% in population. The patients with GERD usually suffer from epigastric burning, chest compression and sore throat, which influences their quality of life. So far the most effective therapy for GERD is proton-pump inhibitor (PPI). The successful cured rates of PPIs for GERD are about 80-90%. However, 40-80% of patients have recurrence of symptoms after stop drug for half to one year. It is necessary to find another safe drug to prevent the recurrence of GERD. Xiangsha-liujunzi-tang (XSLZT) is a Chinese herb drug preparation, which was commonly used in treatment of spleen and stomach qi deficiency in traditional Chinese medicine. Recently, XSLZT was found to be effective in treatment of functional dyspepsia through improvement of gastrointestinal motility. In this study we will observe the effectiveness of XSLZT in augmenting the effect of PPI and preventing the recurrence of GERD. We will include 80 patients with clinical symptoms of GERD and endoscopic findings with reflux esophagitis by a severity of to A or B degree according to the classification of Los Angeles. After signing informed consent, subjects will be randomly divided into two groups. The subjects in treatment group will be given one tablet of Rabeprazole (one kind of PPI) 20mg per day combined with 3.5 grams of concentrated extracted powder of XSLZT after each meal twice per day. The subjects in other group (control group) will be given the same dosage of rabeprazole and starch placebo (containing 1/20 concentration of XSLZT) as treatment group. The therapeutic period will be 16 weeks. During this period, we will evaluate the severity of symptoms in subjects with a questionnaire form for GERD. After then, all subjects will continue to receive therapy as therapeutic period but in place of rabeprazole with Toppal (a kind of anti-acid agent) for 24 weeks to prevent the recurrence of GERD. We will further evaluate the symptoms of patients every 8 weeks until subjects have recurrence of GERD symptoms and endoscopic findings of reflux esophagitis. We will analyze the differences in symptomatic severity and recurrent rates of GERD between two groups by unpaired Student’s t-test. From April 9, 2012 until Nov.30, 2012, we have screened 134 patients with symptoms of reflux esophagitis (degree A and B) under diagnosis by upper gastrointestinal endoscopic examination, and 123 patients agreed to joint clinical trial. Among the subjects, 53 (43.1%) have completed treatmentfor 16 weeks, 31 (25.2%) are still under treatment, and 39 (31.7%) quitted from clinical trial. About 60-70 subjects will joint the 2nd satge of clinical trial for follow-up. So far no severe adverse events were reported in this clinical trial, suggesting the safety for combination of PPI and XSLZT. In 2013, we will continue 16 weeks of therapy and 24 weeks of follow-up for uncompleted studied subjects. We hope that, our studied tram can be supported by DOH to carry out the senceondary stage of clinical trial. We believe that, this study will be helpful in the treatment and prevention for recurrence of GERD and the development of Chinese medicine in clinical application.