Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study (JMMS).

BACKGROUND AND AIM: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD. METHODS: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated. RESULTS: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication. CONCLUSIONS: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.

High prevalence of irritable bowel syndrome in medical outpatients in Japan.

BACKGROUND AND GOALS: The prevalence of irritable bowel syndrome (IBS) among Japanese patients who visit hospitals departments of internal medicine is thought to be high. However, no clear statistical evidence has been provided to support such a claim. We tested the hypotheses that the prevalence of IBS in medical outpatients clinics in Japan is high, and that IBS patients feel more psychosocial stress than patients without IBS. STUDY: The subjects in this study were 633 patients who visited participating physicians. Patients were asked to fill in the Japanese version of the Rome II Modular Questionnaire (RIIMQ) for IBS diagnosis, the Self-reported Irritable Bowel Syndrome Questionnaire (SIBSQ) for severity of the disease and the demographic questionnaire for perceived stress and life style. RESULTS: Rome II-defined IBS was diagnosed in 196 patients (31%). Analysis of variance revealed significant difference in the IBS scores of SIBSQ among IBS subjects (39.0+/-11.1, mean+/-SD), functional bowel disorder subjects (27.1+/-10.2), and normal subjects (24.0+/-10.0, P<0.01). The prevalence of IBS depending on age formed 2 peaks, one among adolescents and the other among the elderly. IBS patients had significantly more perceived stress (P<0.0001), irregular sleep habit (P<0.0001), and irregular meal habit (P<0.0001) than those without IBS. CONCLUSIONS: The prevalence of IBS among medical outpatients in Japan is high (31%). IBS subjects among medically ill patients are thought to have more perceived stress and less regular life styles.

A randomized, double-blind, placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome is characterized by abdominal discomfort and/or pain associated with altered bowel habits. The neurotransmitter serotonin and serotonin type 3 receptors that are extensively distributed on enteric neurons in the human gastrointestinal tract play a role in increasing the sensation of pain and affecting bowel habits in patients with irritable bowel syndrome. The aim of this study was to evaluate the efficacy and safety of the serotonin type 3 receptor antagonist ramosetron hydrochloride in Japanese patients with diarrhea-predominant irritable bowel syndrome. MATERIAL AND METHODS: In a double-blind, placebo-controlled, parallel group-comparative study with a 1-week run-in period, 539 patients with diarrhea-predominant irritable bowel syndrome meeting the Rome II diagnostic criteria received either 5 microg ramosetron hydrochloride (n=270) or placebo (n=269) once daily for 12 weeks. RESULTS: Forty-seven percent of ramosetron hydrochloride-treated patients were monthly responders in the primary end-point, "Patient-reported global assessment of relief of irritable bowel syndrome symptoms", compared with 27% for placebos (p<0.001). The most frequently reported adverse event in the ramosetron hydrochloride-treated group compared with the placebo group was hard stool. CONCLUSIONS: Ramosetron hydrochloride 5 microg once daily is effective and well tolerated in the treatment of abdominal pain, discomfort and bowel habits in patients with diarrhea-predominant irritable bowel syndrome.

Efficacy of a Low-Dose Omeprazole-Based Triple-Therapy Regimen for Helicobacter pylori Eradication Independent of Cytochrome P450 Genotype : The Japanese MACH Study.

OBJECTIVES: To investigate the efficacies of two different triple-therapy regimens (standard versus low doses), and the influence of cytochrome P450 enzyme (CYP) genetic polymorphism on these efficacies, in Japanese patients undergoing Helicobacter pylori eradication treatment. METHODS: All patients received 1 week of triple therapy. Patients in group A (low-dose regimen) received omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day; patients in group B (standard-dose regimen) received omeprazole 40 mg/day + amoxicillin 2000 mg/day + clarithromycin 1000 mg/day. RESULTS: A total of 225 patients (113 in group A and 112 in group B) were randomised to one of the two triple-therapy regimens. The eradication rates were 78.8% (89/113 patients; 95% CI 70.1, 85.9) in group A and 83.0% (93/112 patients; 95% CI 74.8, 89.5) in group B. Genetic polymorphism of CYP2C19, a major metabolic enzyme of omeprazole, did not affect eradication rates, while susceptibility to clarithromycin greatly affected the success of eradication. The cumulative ulcer relapse rate at 24 weeks after endoscopically documented ulcer healing (30 weeks after completion of the drug regimen) was 8.3% for group A and 12.5% for group B (log rank test: p = 0.6248). However, comparison of the cumulative relapse rate of 6.7% in patients after successful H. pylori eradication with the relapse rate of 27.3% in those who failed H. pylori eradication revealed a significant difference in the remission-time curve (log rank test: p = 0.0047). This finding suggested the existence of a relationship between H. pylori eradication failure and ulcer relapse. Both drug regimens were well tolerated. Endoscopically proven reflux esophagitis developed in about 10% of patients after eradication, but was not clinically significant. CONCLUSIONS: One week of triple therapy with a low-dose regimen provides adequate H. pylori eradication in Japanese patients. CYP genetic polymorphism is of minimal clinical significance with both triple-therapy regimens.

[GERD: guidance in changing life-style].

Gastroesophageal reflux disease (GERD) is increasing due to adoption of a western life style and an aging society in recent years. The symptoms of GERD, such as heartburn, regurgitation of gastric contents into the mouth, and chest pain, decrease QOL, and continuous treatment is necessary. Treatment of GERD is mainly drug therapy; however, it is believed that providing guidance in changing life-style and providing information about the disease will permit long-lasting relief of the symptoms.