N-3 Polyunsaturated Fatty Acids Prevent Postoperative Recurrence of Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
Crohn's disease (CD) is a chronic recurrent intestinal inflammation involving the whole digestive tract, with high disability rate, high surgical rate and high recurrent rate postoperatively. Preventing postoperative recurrence in CD patients is an important clinical problem needed urgent intervention. Azathioprine (AZA) and infliximab (IFX) effectively prevent postoperative recurrence in CD patients, but the postoperative recurrence rate is still as high as 41%. Oral supplement of n-3 polyunsaturated fatty acids (n-3 PUFA) owns the advantages of high compliance and low economic cost. We aim to evaluate the effect of routine treatment (AZA/IFX) combined with long-term dietary n-3PUFA on the prevention and treatment of postoperative recurrence of CD, which help optimize the treatment strategy for the prevention of postoperative recurrence.

Official Title
-----------------
N-3 Polyunsaturated Fatty Acids Prevent Postoperative Recurrence of Crohn's Disease：a Prospective Randomized Controlled Trial

Conditions
-----------------
Inflammatory Bowel Diseases, Crohn Disease, Polyunsaturated Acid Lipidosis

Intervention / Treatment
-----------------
* Drug: azathioprine
* Drug: infliximab
* Drug: N-3 Polyunsaturated Fatty Acids


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: CD patients undergoing partial resection，anastomosis or enterostomy. age ≥18 to ≤80 years; have indications of AZA or IFX application (according to the consensus of ECCO 2016 years); Preoperative diagnosis CD, must provide the biopsy pathological record which accords with the CD diagnosis; If the subject is a woman of childbearing age, pregnancy tests must be conducted at baseline to exclude pregnancy, and the trial process must follow the contraceptive advice of this project subjects must be able and willing to provide written informed consent and comply with the requirements of this research program Exclusion Criteria: patients without indications use of AZA or IFX; isolated colon CD patients; patients who can't take long-term oral intervention of n-3PUFA; patients diagnosed with short bowel or short bowel syndrome; patients with severe, progressive or uncontrolled kidney, liver, blood or endocrine diseases; postoperative abdominal infection, anastomotic fistula and other complications; there's an infection, Such as Clostridium difficile toxin or other intestinal pathogens infection, active tuberculosis or intestinal tuberculosis, human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C; patients with a history of gastrointestinal dysplasia; patients with TPMT gene mutations or low activity; patients who has already participated in other clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: n-3PUFA treatment group<br>On the basis of routine treatment, oral supplement of n-3PUFA was given to CD patients since 2-week-postoperative till 1-year-postoperative. | Drug: azathioprine<br>* daily orally<br>* Other names: AZA;Drug: infliximab<br>* intravenously, at 0, 2,6 weeks with every 8-week-interval later<br>* Other names: IFX;Drug: N-3 Polyunsaturated Fatty Acids<br>* Ethyl polyenoate capsule is given as drug intervention. The main components are ethyl eicosapentaenoate (EPA-E) and ethyl docosahexaenoate (DHA-E), both of which will transform into ethyl eicosapentaenoate (EPA) and ethyl docosahexaenoate (DHA). Drug dose is 0.25 g EPA-E&DHA-E; per capsule one at a time, Three times a day.<br>* Other names: n-3PUFA;|
| Placebo Comparator: Conventional treatment group<br>Treatment of azathioprine (daily orally) or infliximab (intravenously, at 0, 2,6 weeks with every 8-week-interval later) was given since 2-week-postoperative till 1-year-postoperative. | Drug: azathioprine<br>* daily orally<br>* Other names: AZA;Drug: infliximab<br>* intravenously, at 0, 2,6 weeks with every 8-week-interval later<br>* Other names: IFX;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year postoperative anastomotic recurrence rate | anastomotic recurrence including endoscopic recurrence and imaging recurrence | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 months postoperative anastomotic recurrence rate | anastomotic recurrence including endoscopic recurrence and imaging recurrence | 3 months | 
| clinical recurrence rate | CDAI score larger than 150 | 3 months，1 year | 
| Inflammatory load | level of serum C- reactive protein | 3 months，1 year | 
| Inflammatory load | level of serum fecal calprotectin | 3 months，1 year | 
| Life quality SF-36 | inflammatory bowel disease questionnaire and health survey summary table SF-36 | 3 months，1 year |