z-338 and Gastroesophageal-Reflux

Dyspepsia affects up to 40% of the general population and significantly reduces quality of life. A small proportion of patients have peptic ulcer disease as cause and this can be treated empirically with Helicobacter pylori eradication therapy in those that are infected. Approximately 20% have gastro-oesophageal reflux disease and this can be effectively treated with proton pump inhibitor therapy. Patients who remain symptomatic may warrant an endoscopy, but most will have functional dyspepsia. Treatment of functional dyspepsia remains a challenge.. Recent large randomized trials suggest tricyclic antidepressant therapy may be effective in functional dyspepsia. A phase III randomized controlled trial reports that a new prokinetic, acotiamide, reduces dyspepsia symptoms in functional dyspepsia patients. There are also preliminary data that suggest buspirone, a drug that promotes gastric accommodation, is also effective in functional dyspepsia. There are also data to suggest that functional dyspepsia is caused by subtle manifestations of inflammation in the upper gastrointestinal tract, possibly caused by food sensitivity or a change in gut flora.. The initial management of dyspepsia is well established, but managing those with continued symptoms is a challenge. Antidepressants and newer gastric motility agents show promise. Targeting the diet and gut microbiome is another area for future research in functional dyspepsia.

Topics: Antidepressive Agents, Tricyclic; Benzamides; Diet; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Peptic Ulcer; Probiotics; Thiazoles

Approximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief.. This study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD.. This was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible.. Seventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes.. Adding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.

Topics: Adult; Aged; Aged, 80 and over; Benzamides; Double-Blind Method; Drug Therapy, Combination; Esophageal pH Monitoring; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Japan; Male; Manometry; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Remission Induction; Thiazoles; Time Factors; Treatment Outcome; Young Adult

Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) often coexist or overlap. In this study, the efficacy of acotiamide in combination with a standard dose of rabeprazole for GERD and FD was compared with that of a double dose of rabeprazole.. Patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose proton pump inhibitor (PPI) for ≥ 8 weeks were randomized into two groups and received either acotiamide 300 mg/day + rabeprazole 10 mg/day or rabeprazole 20 mg/day for 4 weeks. Efficacy was assessed by reductions in symptom scores using the Izumo scale questionnaire and modified F-scale questionnaire.. As the primary endpoint, three upper gastrointestinal symptoms (heartburn, epigastralgia, and epigastric fullness) were reduced by ≥ 50% in 40.8% and 46.9% of patients in the combination and PPI double-dose groups, respectively, with no significant difference between the two groups. Essentially similar results were obtained for the modified F-scale questionnaire. No serious adverse events were noted.. Acotiamide 300 mg/day in combination with rabeprazole 10 mg/day or rabeprazole 20 mg/day relieved symptoms in patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose PPI for ≥ 8 weeks, and the efficacies did not differ between the two treatments. The combination therapy may be an alternative option for persistent symptoms in these patients.

Topics: Aged; Benzamides; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyspepsia; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Rabeprazole; Surveys and Questionnaires; Thiazoles; Time Factors; Treatment Outcome

Currently, there is no study evaluating the effect of acotiamide on transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to evaluate the effect of acotiamide on TLESRs using simultaneous high-resolution manometry (HRM) and impedance-pH monitoring.. Ten healthy subjects were enrolled. On day 1, subjects underwent HRM and impedance-pH recordings as a baseline. Subjects ate a 750-kcal liquid meal; recording was continued for 2 h while the subjects were in a sitting position. After the administration of acotiamide 100 mg three times a day for 1 week, subjects underwent HRM and impedance-pH recording under the same protocol.. A total of 208 TLESRs were identified at baseline. Acotiamide decreased the total number of TLESRs from 208 to 143 (p < 0.05). The rate of reflux events during TLESRs after acotiamide administration was similar to that at baseline (57% after acotiamide vs. 58% at baseline). Bolus clearance time was significantly reduced by acotiamide.. Acotiamide was believed to have the potential for reducing TLESRs and for enhancing esophageal bolus clearance in healthy volunteers. Future research is needed to determine whether the effects of acotiamide that reduce TLESRs and enhance esophageal motility could improve symptoms in patients with refractory gastroesophageal reflux disease.

Topics: Adult; Benzamides; Electric Impedance; Esophageal Sphincter, Lower; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Gastrointestinal Motility; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Male; Manometry; Muscle Relaxation; Thiazoles

Functional dyspepsia (FD) is a gastroduodenal disorder that presents as postprandial fullness, early satiation, or epigastric burning despite no evidence of a structural disease. Proton pump inhibitors (PPIs) are often the first choice for treating FD. However, some patients need additional medication because of residual symptoms despite a certain level of benefit from the PPI. For these patients, a combination of PPI and other agents has a possibly more beneficial effect than changing their medication. This study aimed to evaluate the efficacy of an initial PPI followed by combination therapy with PPI and acotiamide in FD patients with residual symptoms after an initial PPI. We enrolled 105 patients who started an initial PPI (20 mg of esomeprazole once a day). Twenty-three patients with residual symptoms received 100 mg of acotiamide, a cholinesterase inhibitor, three times a day with esomeprazole as a combination therapy for 2 weeks. The symptoms were evaluated using the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSG). Eighteen of 23 patients (78%) achieved an overall improvement in symptoms. Almost all FD-related symptoms statistically improved after the combination therapy, with an improvement in the mFSSG score relevant to the postprandial distress syndrome and epigastric pain syndrome. The symptoms improved regardless of age, sex, and the pre-combination therapy score of the mFSSG. Our findings suggest that the combination therapy of acotiamide and PPI may be effective in selected FD patients with insufficient improvement with an initial PPI. However, well-designed trials are required to confirm the efficacy.

Topics: Benzamides; Drug Resistance; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Thiazoles; Treatment Outcome

The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved: 61% vs 80%, p=0.029 and resolved: 17% vs 33%, p=0.069). We then evaluated the effect of acotiamide on epigastric pain syndrome (EPS) (n=33) and postprandial distress syndrome (PDS) (n=41). Acotiamide treatment showed an early effect on rates of improvement (63%) and resolution (42%) of EPS symptoms at one month, maintained up to three months (69% and 39%, respectively). Both rates of improvement and resolution of PDS symptoms showed a significant increase from one month to three months (56% vs 78%, p=0.021 and 17% vs 46%, p=0.004, respectively). The severity of functional dyspepsia symptoms before treatment was significantly associated with failed resolution of functional dyspepsia symptoms (p=0.013). Acotiamide improves and resolves EPS symptoms as well as PDS symptoms. PDS symptoms take longer to resolve than EPS symptoms. J. Med. Invest. 63: 230-235, August, 2016.

Topics: Abdominal Pain; Adult; Aged; Benzamides; Dyspepsia; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Postprandial Period; Quality of Life; Retrospective Studies; Syndrome; Thiazoles

The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux.. Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer.. Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time.. Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance.. This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260.

Topics: Adult; Benzamides; Cross-Over Studies; Electric Impedance; Esophageal pH Monitoring; Esophageal Sphincter, Lower; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Healthy Volunteers; Humans; Male; Manometry; Peristalsis; Postprandial Period; Thiazoles; Young Adult