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

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

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.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: pectin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Department of Generay Surgery, Jinling hosptal, Medical School of Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jinling Hospital, China
• Investigators: Principal Investigator: Jianfeng Gong, MD, Department of general surgery,Jinling hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 13, 2014
• First Posted (Estimate): June 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 14, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Dietary fiber
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: Pectin-2014