Mechanism of PERK - eIF2a Pathways in Intestinal Mucosal Barrier of IBS-D and the Role Metabolism Ingredients of Tongxieyaofang

Study Overview
=================
Brief Summary
-----------------
Diarrhea irritable bowel syndrome(IBS-D）has seriously affected health and quality of life of patients.It may be important pathogenesis in development and recurrence of the process of IBS-D,excessive endoplasmic reticulum stress (ERS) activated PERK(proteinkinaseR-like ERkinase，PERK)-eIF2a(eukaryotic translation initiation factor 2 alpha,eIF2a) pathway and damaged intestinal mucosal epithelial Barrier. Tongxieyaofang(TXYF) had obtained satisfactory effect in treating IBS-D in clinic and previous study, but it is unknown that herbal formula how to work.This project applies metabolomics method to detect plasma,urine and stool metabolites for patients before and after treatment, to determine the effects of themultiple ingredientsof TXYF in body.

Official Title
-----------------
Mechanism of PERK - eIF2a Pathways in Intestinal Mucosal Barrier of IBS-D and the Role Metabolism Ingredients  of Tongxieyaofang

Conditions
-----------------
IBS (Irritable Bowel Syndrome)

Intervention / Treatment
-----------------
* Drug: Tongxieyaofang(granule)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients meeting the diagnostic criteria of Western medicine for IBS-D; aged 18-70 years old; with a baseline IBS-SSS score over 75 points; voluntarily signed the informed consent; local resident who could ensure follow-ups, with basic reading ability Exclusion Criteria: Patients with IBS-C, -M, and uncertain forms; accompanied with serious lesions in major organs including heart, liver, and kidney, hematopoietic system diseases, and tumors; gastrointestinal organic disease (e.g., chronic pancreatitis), or systemic diseases affecting the digestive tract motion (e.g., hyperthyroidism,diabetes, chronic renal insufficiency, and nervous system diseases); undergoing or requiring constant use of drugs that may affect gastrointestinal functions (e.g., anti-cholinergic drugs, calcium channel blockers, 5-HT3 receptor antagonist, antidiarrheal agents, antacids, prokinetic agents, antidepressants, anxiolytics, and intestinal flora regulating drugs); with history of abdominal surgery (e.g., cholecystectomy); with an allergy history of tested drugs or severe allergy history of food; pregnant and lactating female; with a history of neurological or psychiatric disorders; or participating in other clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: health control group<br> | |
| Experimental: Tongxieyaofang granule group<br> | Drug: Tongxieyaofang(granule)<br>* Take this granule twice a day,one bag for each time,one hour after a meal,for 4 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Irritable Bowel Syndrome Symptom Severity(IBS-SSS) scale | Patients are graded according to their own symptoms（abdominal pain，bloating，defecation satisfaction，the extent to which the disease affects the lives of patients，bowel movements）, the total score less than 75 points was considered as in remission, 75 175 as mild, 175 300 as moderate, and over 300 as severe. We will assess changes in patient scores before and after treatment to reflect the extent of disease remission. | IBS-SSS was evaluated by patients at 4th week | 
| Bristol stool form scale（BSFS） | Different fecal types can reflect different intestinal transit times, the lower the score, the longer the transmission time; the higher the score, the shorter the transmission time. We will assess changes in scores before and after treatment to reflect the extent of disease remission. | BSFS was evaluated by patients at 4th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IBS-D PRO( patient reported outcomes) Scale | Grading from the field of physiology, independence, and psychology，Use score changes to assess improvement in all areas of the patient.Minimum score is 0，means no symptoms，maximum score is 144，means all symptoms are severe. | IBS-D PRO Scale was evaluated at 4th week | 
| SF-36(the MOS item short from health survey)Scale | Score evaluation from 8 aspects: physical function, role-physical, pain, global health status, vitality，social function,role-emotional， mental health.Use score changes to assess improvement in all areas of the patient. Maximum score is147.The higher the score, the better the status in all aspects. | SF-36 Scale was evaluated at 4th week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBS-D