Effect of Soluble Dietary Fiber on Bacterial Translocation in Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of soluble dietary fiber on bacterial translocation and mucosal immunology in patients with Crohn's disease.

Detailed Description
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Bacterial translocation (BT) is a proposed mechanism of CD. Microorganisms can be cultured from 18-48% of draining mesenteric lymph nodes from CD patients. A breakdown in barrier function in late stage CD has been observed in patients requiring surgery. In addition, it was found that BT influences the response to biological therapy and clinical relapse in CD. Therefore, reducing BT may be of therapeutic importance in treatment for CD. The role of soluble dietary fiber in Crohn's disease (CD) is still inconclusive. Population based studies have shown that long-term intake of dietary fiber is associated with lower risk of CD. However, meta-analysis did not show benefit in inducing or maintaining remission. In addition, the possible mechanism of dietary fiber on CD is still unclear. The rationale relates to the beneficial effects of fiber may be due to the production of the fiber metabolites short-chain fatty acids (SCFAs), particularly butyrate. Dietary substrates may modify the commensal microbiota or their metabolites or enhance epithelial barrier function. Recently, it was found that dietary fiber metabolites SCFA is regulatory of mucosal regulatory T cells. The current study is to examine the impact of dietary fiber on bacterial translocation,intestinal luminal microbiology, and mucosal immunology in CD patients.

Official Title
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A Randomized, Controlled Study of Soluble Dietary Fiber on Bacterial Translocation in Adults Patients With Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: pectin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged >=17 years with diagnosis of CD for at least 3 months defined by histology or radiology ileocolonic non-penetrating disease Moderate active CD with CDAI 250-450 CRP level over normal range Stable CD therapy with a total steroid dose not exceeding 10mg prednisolone or equivalent for 4 weeks Exclusion Criteria: Infection with enteric pathogen Usage of probiotics, antibiotics, or prebiotics within the last month Change in dose of oral steroids or 5-ASA within the last 4 weeks or AZA or MTX in the last 3 months Dose of steroids exceeds 10 mg prednisolone per day or equivalent Infusion of IFX or any alternative biological therapy within the last 3 months Use of rectal 5-ASA or steroids within the last 2 weeks. Imminent need for surgery or presence of severe disease (CDAI >450) Pregnancy or lactation Short bowel syndrome or subtotal/total colectomy Pure anal disease and previous proctocolectomy Significant hepatic, renal, endocrine, respiratory, neurological or cardiovascular disease as determined by the principal investigator History of cancer with a disease-free state of less than two years Patients with penetrating disease or small bowel lesion only.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pectin<br>Patients allocated to experiment group will receive standard enteral nutrition formula(Fresubin) supplemented with 15g pectin each day for 4 weeks. | Drug: pectin<br>* Patients allocated to experiment group will receive 15g pectin each day<br>* Other names: soluble dietary fiber;|
| Placebo Comparator: control<br>Patients allocated to control group will receive standard enteral nutrition formula(Fresubin) for 4 weeks | Drug: pectin<br>* Patients allocated to experiment group will receive 15g pectin each day<br>* Other names: soluble dietary fiber;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bacteria translocation in MLN, mesenteric fat and peripheral blood | Bacterial translocation to mesenteric lymph nodes (MLN),mesenteric fat and peripheral blood during laparotomy before surgical mobilization, as determined by DGGE. | 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of fecal bacteriology | fecal microbiology before and 4 weeks after pectin treatment, as determined by DGGE | baseline, week 4 | 
| change of fecal SCFA | fecal short chain fatty acid (SCFA) levels before and 4 weeks after treatment, as determined by HPLC. | baseline, week 4 | 
| clinical response | the percentage of patients achieving a clinical response (fall in CDAI of >=70 points) at week 4. | up to 4 weeks after treatment | 
| change of mucosal Treg numbers | mucosal Treg（FoxP3+CD4+）cell number before and after treatment,as determined by immunofluorescence | baseline, week 4 | 
| adverse events | gastrointestinal symptoms(borborygmi,flatulence,abdominal pain,diarrhea etc) | up to 4 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary fiber