Jianpi Huoxue Recipe in Treating Gastric Premalignant Lesion

Study Overview
=================
Brief Summary
-----------------
This study had adopted the multi-center, randomized and controlled experiment design based on standardized mucosal biopsy and pathohistological operation, as well as therapeutic evaluation methodology. Meanwhile, patients diagnosed with chronic atrophic gastritis accompanying with low grade intraepithelial neoplasia and indefinite dysphasia (grade C2/C3 of Vienna classification) confirmed by gastroscopic histopathology were enrolled as the objects of study, while folic acid was used as the control. The therapeutic effect and safety of Jianpi Huoxue Recipe (Moluodan + Sanchi powder) in intervening the gastric Premalignant lesion were evaluated from the points of view of pathology, gastroscopy and symptoms. The elimination rate of intraepithelial neoplasia of gastric mucosa was expected to be improved by 9-12%. Moreover, high quality evidence-based medical evidence regarding traditional Chinese medicine (TCM) in intervening gastric Premalignant lesion would be obtained, which could form the mature, propagable and effective scheme.

Detailed Description
-----------------
Intraepithelial neoplasia of gastric mucosa is a well-recognized gastric Premalignant lesion, which is the key of secondary prevention for gastric cancer. However, no universally acknowledged effective therapeutic scheme is available at present. Previously, the investigator's research group has carried out clinical trial study based on solving the key problems such as diagnostic criteria, mucosal biopsy consistency and therapeutic evaluation methodology, and has attained certain achievements. This study had adopted the multi-center, randomized and controlled experiment design based on standardized mucosal biopsy and pathohistological operation, as well as therapeutic evaluation methodology. Meanwhile, patients diagnosed with chronic atrophic gastritis accompanying with low grade intraepithelial neoplasia and indefinite dysphasia (grade C2/C3 of Vienna classification) confirmed by gastroscopic histopathology were enrolled as the objects of study, while folic acid was used as the control. The therapeutic effect and safety of Jianpi Huoxue Recipe (Moluodan + Sanchi powder) in intervening the gastric Premalignant lesion were evaluated from the points of view of pathology, gastroscopy and symptoms. The elimination rate of intraepithelial neoplasia of gastric mucosa was expected to be improved by 9-12%. Moreover, high quality evidence-based medical evidence regarding traditional Chinese medicine (TCM) in intervening gastric Premalignant lesion would be obtained, which could form the mature, propagable and effective scheme. At the same time, molecular and biological indicators, including CDX2, SOX2, MUC2, MUC6, MUC5AC and CD10, were detected using the pathological tissues, so as to explore the therapeutic mechanism of Jianpi Huoxue Recipe in intervening gastric Premalignant lesion, and to construct the model platform for special disease research on gastric Premalignant lesion.

Official Title
-----------------
Therapeutic Mechanism of Jianpi Huoxue Recipe in Treating Gastric Premalignant Lesion：A Multi-center, Randomized and Controlled Experiment

Conditions
-----------------
Gastric Precancerous Condition

Intervention / Treatment
-----------------
* Drug: MoLuoDan
* Drug: Sanchi powder
* Drug: Folic Acid Tablet
* Drug: MoLuoDan simulation
* Drug: Sanchi powder simulation
* Drug: Folic Acid Tablet simulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients and inpatients diagnosed with chronic atrophic gastritis accompanying with low grade intraepithelial neoplasia and indefinite dysphasia confirmed by gastroscopy and histopathological examination; Patients aged from 18-75 years; Subjects who were informed and voluntarily signed the informed consent. Exclusion Criteria: Patients pathohistologically diagnosed with high grade intraepithelial neoplasia/severe dysplasia; Patients with a history of gastric ulcer, gastric polyps and gastric surgery; Patients taking NSAIDs for a long term; Patients suspected of gastric cancer or malignant lesions in other systems; Patients with a history of gastric surgery; Patients with concurrent primary diseases in cardiovascular, cerebrovascular, liver, kidney and hemopoietic systems (ALT>80 u/L, and/or AST>80 u/L, with abnormal renal function) Patients with mental disease, dysgnosia and logopathy; Pregnant women, or those preparing a pregnancy and breastfeeding women; Patients with a allergic history of medicines used in this experiment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MoLuoDan and Sanchi powder group<br>Experiment group: oral administration of Moluodan concentrated pills with warm water before meal for 8 pills each time for three times a day, + oral administration of Sanchi powder mixing with warm water before meal for 3g each time for twice a day, + oral administration of Folic Acid Tablet simulation half a hour after meal for 5 mg each time for 3 times a day. The medication period was 24 weeks. | Drug: MoLuoDan<br>* oral administration of Moluodan concentrated pills with warm water before meal for 8 pills each time for three times a day<br>Drug: Sanchi powder<br>* oral administration of Sanchi powder mixing with warm water before meal for 3g each time for twice a day<br>Drug: Folic Acid Tablet simulation<br>* oral administration of folic acid simulation tablets half a hour after meal for 5 mg each time for 3 times a day.<br>|
| Active Comparator: Folic Acid Tablet group<br>Control group: oral administration of Moluodan simulation medicine with warm water before meal for 8 pills each time for three times a day, + oral administration of Sanchi powder simulation medicine mixing with warm water before meal for 3g each time for twice a day, + oral administration of folic acid tablets half a hour after meal for 5 mg each time for 3 times a day. The medication period was 24 weeks. | Drug: Folic Acid Tablet<br>* oral administration of folic acid tablets half an hour after meal for 5 mg each time for 3 times a day.<br>Drug: MoLuoDan simulation<br>* oral administration of Moluodan simulation medicine with warm water before meal for 8 pills each time for three times a day<br>Drug: Sanchi powder simulation<br>* oral administration of Sanchi powder simulation medicine mixing with warm water before meal for 3g each time for twice a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The disappearance rate of dysplasia | The all patients' histopathology will be evaluated two times, the first time is when the patients' are included into the clinical trials, the second time is after 24 weeks treatment in each group, patients' histopathology should be evaluated for comparison between two groups,at the same time patients' histopathology should be evaluated for comparison in each group.The change in histological score (mean score of all biopsie after treatment in each group and between groups was calculated. The response rate of each pathological lesion was calculated as a percentage of those improved or disappeared at the 6th month to all subjects. The disappearance rate of dysplasia between groups were compared, which was defined as the absence of dysplasia (score 0) in all biopsy specimens after treatment. | six months | 
| The score changes of histopathology | The score changes of atrophy, intestinal metaplasia, chronic inflammation and active inflammation compared between baseline and after 6-month treatment. | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The score changes of Endoscopic Findings | The score changes of endoscopic findings, such as erosion, bleeding, coarse and uneven mucosa, and bile reflux were compared between baseline and after 6-month treatment. | six months | 
| Main symptom score | Changes of symptom score were compared. The symptom include upper abdominal pain, upper abdominal distension, poor appetite, nausea and belching. The disappearance rate of symptom was expressed as a percentage of the subjects whose symptoms disappeared after medication to those exhibiting symptoms before medication. | six months | 
| The patient-reported outcome (PRO)scale integrals | The patient-reported outcome (PRO) instrument for chronic gastrointestinal diseases was a 35-item instrument, including 6 dimensions of regurgitation, dyspepsia, defecation, general condition, emotion and social function. All items graded into 5 levels and scored 0-4, except for decreased appetite, which is grouped into 4 levels and scored 0-3. | six months |