Functional dyspepsia is a chronic condition in which dyspepsia such as postprandial fullness, early satiety, epigastric pain or heartburn without organic abnormalities has been identified. So far, a clear pathologic mechanism has not been identified. Worldwide, the morbidity rate of functional dyspepsia is reported to be 5-11%, and although it is not a direct life-threatening disease, more than 50% of them are reported to be disturbing their daily lives, which is very important socioeconomic disease. In conventional medicine, various therapeutic agents are administered individually or in combination with the aim of relieving symptoms, but it is rare that a clear effect is shown. Therefore, the demand for complementary and alternative therapies such as herbal medicines is increasing around the world. According to a survey conducted on 349 clinical Korean medicine doctors in June-July 2017, Yukgunja-tang was widely used for the treatment of functional dyspepsia, following (Hyangsa)Pyeongwisan (30%) and Banhasasim-tang (27%). In particular, (Hyangsa)Pyeongwisan and Banhasasimtang are herbal medicines of insurance coverage, and therefore, Yukgunja-tang is the most widely used herbal medicine of non-insurance coverage. In addition, clinical studies of Yukgunja-tang on functional dyspepsia have been actively conducted in Japan and China, but in Korea, in addition to studies to verify the clinical effects of Yukgunja-tang according to specific shape types in patients with functional dyspepsia, no large-scale clinical trials reflecting the clinical field have been conducted. According to a recent systematic review of the literature on functional dyspepsia of Yukgunja-tang, Yukgunja-tang as a complementary and alternative medicine can be considered as an effective and safe treatment for functional dyspepsia, but the evidence is uncertain due to the low quality of the included studies. Therefore, a high-quality randomized controlled clinical trial is needed to verify the effectiveness of Yukgunja-tang on functional dyspepsia.

Treatment

Oral administration of Yukgunja-tang or Pyeongwi-san, or usual care for 6 weeks

Arm Label

Target Number of Participant

Arm Type

Arm Description

Oral administration of Yukgunja-tang for 6 weeks, 2 times a day before or between meals

Arm Label

Target Number of Participant

Arm Type

Arm Description

Oral administration of Pyeongwi-san for 6 weeks, 3 times a day before or between meals

Arm Label

Target Number of Participant

Arm Type

Arm Description

Usual care for 6 weeks

Gender

Age

Description

(1) adults aged 19-75 years at the screening visit 
(2) according to Rome IV criteria, one or more of postprandial fullness, early satiety, epigastric pain, and epigastric heartburn without organic findings occurred at least 6 months ago and the symptoms persist for the last 3 months or more
(3) the intensity of dyspepsia measured by 0-100mm visual analogue scale is 40 points or more
(4) those who have voluntarily signed written informed consent approved by the institutional review board, after sufficient explanation of this study

(1) those who have been diagnosed with organic diseases such as peptic ulcer, esophageal cancer, MALT lymph cancer, stomach cancer, colon cancer, biliary tract and pancreatic disease (except asymptomatic cholelithiasis), inflammatory bowel disease, etc. within 1 year prior to screening
(2) when the symptoms of reflux esophagitis and irritable bowel syndrome are more severe than those of dyspepsia
(3) in case of severe weight loss, bloody stool, dysphagia, swallowing pain, persistent vomiting, and other alarm symptoms
(4) those who have been diagnosed with mental disorders such as major depressive disorder, anxiety disorder, panic disorder, or have a depression score of 11 or higher on the Hospital Anxiety and Depression Scale
(5) those who have a serious structural disease (e.g., heart, lung, liver, kidney disease, malignant disease)
(6) those with a history of gastrointestinal surgery (in the case of appendectomy, if 6 months have passed since surgery, they can participate in clinical trials)
(7) taking proton pump inhibitors, histamine receptor antagonists, antacids, prokinetics, antidepressants, fundus relaxant, mucosal protecting agents, nonsteroidal anti-inflammatory drugs, aspirin, anticholinergic drugs, or oral steroids or receiving Helicobacter eradication treatment that can affect the gastrointestinal tract within 2 weeks prior to screening (however, taking low-dose aspirin (100 mg/day or less) for the purpose of preventing cardiovascular disease is allowed)
(8) those who have received Korean medicine treatments such as acupuncture, herbal medicine, or moxibustion for the purpose of improving dyspepsia within 2 weeks prior to screening, or who are planning to receive treatment during the study period
(9) severe liver or renal disease (aspartate aminotransferase or alanine aminotransferase levels ≥ 3 times upper limit of normal or creatinine levels ≥ 2 times upper limit of normal) 
(10) participants with a history of alcohol abuse or drug abuse within the past year 
(11) women who are pregnant or lactating, or women who do not agree to use effective methods of contraception during the clinical trial 
(12) participants with genetic problems, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
(13) participants with known hypersensitivity to investigational products 
(14) participants who had taken other investigational products within 3 months 
(15) participants who are judged to be inappropriate for participating this study

Total Dyspepsia Symptom Scale

Week 0, 3, 6, 9, and 24

Single Dyspepsia Symptom Scale

Week 0, 3, 6, and 9

Overall Treatment Effect

Week 3, 6, 9, and 24

Dyspepsia visual analogue scale

Screening, Week 3, 6, and 9

Functional Dyspepsia-related Quality of Life

Week 0, 3 and 6

hospital anxiety and depression scale

Screening, Week 3, 6, and 9

health-related quality of life (EQ-5D-5L)

Week 0, 3, 6, 9, and 24

Spleen qi deficiency questionnaire

Week 0, 3 and 6

Damum questionnaire

Week 0, 3 and 6

serum ghrelin level  (acyl-ghrelin, deacyl-ghrelin, Ratio of acyl-ghrelin to total ghrelin)

Screening, Week 6

liver and renal function, CBC and electrolyte test

Screening, Week 6

Incidence of adverse reaction

every visit

Cost investigation

Week 0, 3, 6, 9, and 24