Clinical trial NCT03320538: Efficacy and Safety of Hou Gu Mi Xi in Patients With Peptic Ulcer Diseases
Official title: Efficacy and Safety of Hou Gu Mi Xi in Patients With Peptic Ulcer Diseases: A Multicenter, Randomized, Double-blinded, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peptic Ulcer Disease
Keywords: Hou Gu Mi Xi
peptic ulcer disease
traditional Chinese medicine
randomized controlled trial
dietary therapy
Lead sponsor: Jiangxi University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: Jiangxi Hospital of Traditional Chinese Medicine
name: The First Affiliated Hospital of Nanchang University
name: Second Affiliated Hospital of Nanchang University
name: The Third Affiliated Hospital of Nanchang University
name: Nanchang Hongdu Hospital of Traditional Chinese Medicine
name: Nanchang Hospital of Integrated Traditional Chinese and Western Medicine
name: The Nanchang Third Hospital
name: Xinyu People's Hospital
name: Xinyu Hospital of Traditional Chinese Medicine
name: Jiujiang No.1 People's Hospital
name: Jiujiang Hospital of Traditional Chinese Medicine
First posted: 2017-10-25
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial aims to determine whether Jiangzhong Hou Gu® Mi Xi™ is an effective intervention to improve symptoms and indicators in patients with spleen qi deficiency and peptic ulcer diseases.

Detailed description: Peptic ulcer diseases (PUD) is a common kind of digestive system disease, which mostly involves in stomach and duodenum. PUD may occur at any age but mainly at 30 to 49 years (the proportion was about 50% among all PUD patients). One epidemiological survey showed that the incidence was 17.2% in China and the ratio of gastric to duodenal ulcer diseases was about 1:2.

The two most common reasons for causing PUD were infection of Helicobacter pylori (Hp) and long-term use of non-steroid anti-inflammatory drug (NSAID). In recent year, the infection rate of Hp increased continuously. Among Chinese PUD patients, 92.6% infected Hp, and 72.2% patients who infected Hp occurred PUD. The typical symptoms of PUD were upper abdominal pain, abdominal distension, nausea and vomiting, belching, and inappetence. These symptoms were cyclical, rhythmic and chronic, and were usually tolerable. However, PUD may progress to bleeding or perforation, and these acute complication always lead to worse prognosis.

Along with the development of medical science, traditional Chinese medicine (TCM) is playing an increasingly rule in treatment of PUD. Shen Ling Bai Zhu San is a classic Chinese medicinal formulae originally described in Tai Ping Hui Min He Ji Ju Fang in the Fang Song Dynasty (1102 AD), which is composed of ginseng, tuckahoe, atractylodes, baked licorice, coixenolide, Chinese yam, lotus seed, shrinkage fructus amomi, platycodon grandiflorum, white hyacinth bean, and dried orange peel. It is mainly used for treating the syndrome of spleen qi deficiency, including dyspepsia, chest and stomach distress, borborygmus and diarrhea, limb weakness, thin body, sallow complexion, pale tongue with white and greasy coating, and weak and slow pulse, etc.

In the theory of TCM, spleen is the source for producing qi and blood and thus is the root of life. PUD are classed as the syndrome of "Pi Man (fullness)" in TCM, which was caused by spleen qi deficiency, imbalance of rise and fall, and/or stagnation of qi activity. Shen Ling Bai Zhu San could invigorate spleen by supplying spleen and remove wet, nourish the stomach and intestine, and thus improve symptoms of PUD. Pharmacological researches showed that Shen Ling Bai Zhu San could regulate function of anaerobic and aerobic bacteria in gastrointestinal tract; specifically, it could promote growth of probiotics (e.g. bifidobacterium) and inhibit main drug-resistant strains (e.g. enterococcus), and thereby enhance the body's self-healing function of ulcer.

Jiangzhong Hou Gu® Mi Xi™ is a dietary therapy form of Shen Ling Bai Zhu San, of which removes atractylodes and platycodon grandiflorum (two herbs that could not be used as food) from Shen Ling Bai Zhu San, and adds perilla leaf for adapting a dietary therapy. Jiangzhong Hou Gu® Mi Xi™ used the main formula of Shen Ling Bai Zhu San, so that it could theoretically maintain the treatment effects. Although the reliable health effects of Shen Ling Bai Zhu San has been proved in previous studies, Jiangzhong Hou Gu® Mi Xi™ is optimized in formula and its preparations changed from electuary to rice paste, so that its functional mechanism and efficacy may also be different. Therefore, the investigators plan to perform a hospital-based randomized controlled trial, enroll patients from 13 hospitals in Jiangxi Province in China, aims to assess function and safety of Jiangzhong Hou Gu® Mi Xi™ in patients with spleen qi deficiency and PUD.

Eligibility criteria: Inclusion Criteria:

1. Patient should be diagnosed as gastric or duodenal ulcer under endoscope; the diameter of ulcers range from 0.3 to 1.0 cm; no indicator of bleeding or perforation.
2. Patient should be diagnosed as syndrome of spleen qi deficiency, that is, meet 2 main symptoms of spleen deficiency and 2 main symptoms of qi deficiency, or have 2 main symptoms of spleen deficiency, 1 main symptoms of qi deficiency and tongue symptoms as follow:

   * Main symptoms of spleen deficiency: a) poor appetite; b) abnormal stool (loose, diarrhea); c) abdominal distention after meal or at afternoon
   * Main symptoms of qi deficiency: a) fatigue and weak; b) tired mind and taciturnity
   * Secondary symptoms: a) tastelessness, hypodipsia, like hot drink, or polysialia; b) abdominal pain, as a result either patients like warm or press; pain remits after meal or occurs when work; c) nausea and vomiting; d) tightness in stomach; e) abnormal bowel sounds; f) lean or puffiness; g) sallow complexion; h) powerless defecation weakness; i) edema
   * Tongue symptoms: pale or swollen or teeth-printed tongue with thin and white fur
3. Age is between 18 to 70 years
4. Sign the informed consent

Exclusion Criteria:

1. Patients who have complex peptic ulcer (i.e. have gastric and duodenal ulcer meanwhile)
2. Patients who have history of ulcer complications (e.g. bleeding or perforation)
3. Patients who have indicators of ulcer complications, including bleeding (Forrest stage I, IIa and IIb) or perforation (area of ulcer is more than 1 cm).
4. Patients whose ulcer have healed, that is, the ulcer is at healing stage or scarring stage according to the diagnosis criteria in Consensus View of Integrated Chinese and Western Medicine on Diagnosis and Treatment of Peptic Ulcer (2011, Tianjin)
5. Patients who took proton-pump inhibitor more than 3 days within 15 days, or took non-steroid anti-inflammatory drugs for a long term
6. Female patients who are pregnant or breast-feeding, or prepare to pregnant for pregnancy within 2 years
7. Patients who are allergic to sample or sample composition
8. Patients who are allergic to sample or sample composition
9. Patients who have impaired liver function, including one of following condition: a) total bilirubin \> 35 μmol/L; b) alanine transaminase \>2 upper limit of normal (ULN); or c) aspartate aminotransferase \>2 ULN
10. Patients who have impaired kidney function, that is, serum creatinine \>2 ULN
11. Patients who have obviously abnormal electrocardiogram
12. Patients who have stool occult blood, that is, positive result in immunoassay or iron elemental test, and the results continue to be positive after 3 days of vegetarian diet.
13. Patients who undertaken drugs that could damage stomach and intestine, or experienced side effects of dyspepsia for undertaking non-steroidal anti-inflammatory drugs, theophylline, oral antibiotic or potassium supplements within 3 months
14. Patients who are receiving any agents or other intervention for treating his/her gastrointestinal disorder
15. Patients with any malignant tumor
16. Patients who have severe mental disorders so that could not control his/her action and coordinate the treatment in this trial.
17. Patients who are unwilling to provider personal information and enter this trial
18. Patients who cannot understand and sign informed consent

Primary outcomes:
measure: Total effective rate
timeFrame: At baseline, and 12, 26, 52, and 104 weeks
measure: Quality of ulcer healing
timeFrame: At baseline and 12 and 26 weeks
measure: Changes in Spleen Qi Deficiency Symptoms Grading and Quantifying Scale (unit: score on a scale)
timeFrame: At basline and 6, 12, 26, 52 and 104 weeks
Secondary outcomes:
measure: Ulcer area (cm^2)
timeFrame: At baseline and 12, 26, 52 and 104 weeks
measure: Recurrence rate
timeFrame: At baseline and 12, 26, 52 and 104 weeks
measure: Eradication rate of helicobacter pylori
timeFrame: At 12, 26, 52 and 104 weeks
measure: Gastrin-17 (pg/ml)
timeFrame: At baseline and 12, 26, 52 and 104 weeks
measure: Pepsinogen I (ng/ml)
timeFrame: At baseline and 12, 26, 52 and 104 weeks
measure: Pepsinogen II (ng/ml)
timeFrame: At baseline and 12, 26, 52 and 104 weeks
measure: Body weight (kg)
timeFrame: At baseline and 12, 26, and 52 weeks
measure: Body mass index (kg/m^2)
timeFrame: At baseline and 12, 26, and 52 weeks
measure: Adverse events
timeFrame: At 6, 12, 26, 52 and 104 weeks
measure: Severe adverse events
timeFrame: At 6, 12, 26, 52 and 104 weeks
measure: Drug-related adverse events
timeFrame: At 6, 12, 26, and 52 weeks
measure: Withdrawn due to adverse events
timeFrame: At 6, 12, 26, 52 and 104 weeks
Other outcomes:
Locations:
city: Nanchang
country: China
facility: Jiangxi University of Traditional Chinese Medicine
state: Jiangxi
Study officials:
affiliation: Jiangxi University of Traditional Chinese Medicine
name: Weifeng Zhu, Ph.D.
role: STUDY_CHAIR
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