K Tominaga1,2, Y Sakata3, H Kusunoki4, T Odaka5, K Sakurai6, O Kawamura7, A Nagahara8, T Takeuchi1, Y Fujikawa1,2, T Oshima9, M Kato10, T Furuta11, K Murakami12, T Chiba13, H Miwa9, Y Kinoshita14, K Higuchi2, M Kusano7, R Iwakiri3, K Fujimoto3, J F Tack15, T Arakawa16. 1. Premier Developmental Research of Medicine, Osaka Medical College, Osaka, Japan. 2. Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan. 3. Department of Internal Medicine, Saga Medical School, Saga, Japan. 4. Department of General Medicine, Kawasaki Medical School, Kurashiki-city, Okayama, Japan. 5. Odaka Medical and Gastrointestinal Clinic, Chiba, Japan. 6. Hattori Clinic, Kumamoto, Japan. 7. Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Gunma, Japan. 8. Department of Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, Japan. 9. Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. 10. National Hospital Organization Hakodate Hospital, Hakodate, Japan. 11. Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan. 12. Department of Gastroenterology, Oita University Faculty of Medicine, Oita, Japan. 13. Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan. 14. Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Japan. 15. University Hospitals Leuven, Leuven, Belgium. 16. Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND:Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS:FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS:Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.
RCT Entities:
BACKGROUND:Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FDpatients. METHODS:FDpatients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FDpatients to simultaneously treat gastrointestinal and psychological symptoms.