Washed Microbiota Transplantation Improves Nutritional Status of Patients With Crohn's Disease

Washed Microbiota Transplantation Combining Exclusive Enteral Nutrition Contribute to Nutritional Improvement of Patients With Crohns' Disease

Patients with Crohns' disease (CD) are always complicated with malnutrition. Exclusive enteral nutrition (EEN) is an effective treatment to improve nutritional status and induce remission in patients with CD however a reduction in microbiota diversity was the most frequently reported effect of EEN. There was a raised critical question that whether EEN combining microbiota transplantation can bring much more benefits to those CD patients with malnutrition.

Fecal microbiota transplantation (FMT) is an effective way of remodeling microbiota. The improved methodology of FMT in our group since 2014 was different from the traditional manual FMT and was recently coined as washed microbiota transplantation (WMT), which is dependent on the automatic facilities and washing process in a laboratory room with biosafety level 3.

Importantly, the worse nutritional status might decrease the efficacy of FMT. Therefore, there was a raised critical question that when is the proper time to combine WMT for those CD patients requiring EEN. This trial aimed to explore the timing of WMT in CD patients with malnutrition and assess the efficacy and safety of the strategy using WMT combined with EEN in CD patients.

Study Overview

• Status: Unknown
• Conditions: Crohn's Diseases
• Intervention / Treatment: Procedure: WMT; Dietary supplement: EEN

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients aged 18 to 65 years with active CD, as defined by Harvey-Bradshaw Index (HBI) score >4;
2. patients accompanied with malnutrition as assessed by Nutritional Risk Screening 2002 (NRS2002) score ≥ 3 or Patient-Generated Subjective Global Assessment (PG-SGA) score ≥ 4;
3. patients with high compliance.

Exclusion Criteria:

1. accompanying with contraindications of enteral nutrition (EN) such as ileus, active gastrointestinal bleeding and shock;
2. severe comorbidities (e.g., Clostridium difficile infection, diabetes, cancer, cardiopulmonary failure and severe liver and kidney diseases;
3. parenteral infection such as urinary infection, pneumonia, etc;
4. steroids or biologicals use within 6 week;
5. intestinal fibrotic stenosis;
6. patients who are pregnant or going to be pregnant;
7. patients with mental disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early WMT and EEN; WMT (day1), EEN (day1-15)	Procedure: WMT; Washed microbiota transplantation (WMT) through mid-gut; Dietary supplement: EEN; Exclusive enteral nutrition (EEN) through feeding tube
Experimental: Late WMT and EEN; WMT (day8), EEN (day1-15)	Procedure: WMT; Washed microbiota transplantation (WMT) through mid-gut; Dietary supplement: EEN; Exclusive enteral nutrition (EEN) through feeding tube

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
changes in hemoglobin	Day 8 and day 15
changes in albumin and prealbumin in g/L	Day 8 and day 15
changes in lymphocyte count in 10^9/L	Day 8 and day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of clinical remission	HBI score ≤ 4	day 15

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of adverse events	abdominal pain, fever, increased frequency of defecation, etc.	in 1 month following WMT

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Investigators: Study Chair: Faming Zhang, MD; PHD, Nanjing Medical University

Publications and helpful links

General Publications

• Cui B, Feng Q, Wang H, Wang M, Peng Z, Li P, Huang G, Liu Z, Wu P, Fan Z, Ji G, Wang X, Wu K, Fan D, Zhang F. Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol. 2015 Jan;30(1):51-8. doi: 10.1111/jgh.12727.
• Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9.
• Tjellstrom B, Hogberg L, Stenhammar L, Magnusson KE, Midtvedt T, Norin E, Sundqvist T. Effect of exclusive enteral nutrition on gut microflora function in children with Crohn's disease. Scand J Gastroenterol. 2012 Dec;47(12):1454-9. doi: 10.3109/00365521.2012.703234. Epub 2012 Sep 28.
• Xiang L, Yu Y, Ding X, Zhang H, Wen Q, Cui B, Zhang F. Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study. Front Med (Lausanne). 2021 Oct 22;8:666062. doi: 10.3389/fmed.2021.666062. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: August 14, 2016
• First Submitted That Met QC Criteria: September 7, 2016
• First Posted (Estimate): September 13, 2016

Study Record Updates

• Last Update Posted (Actual): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: fecal microbiota transplantation; malnutrition; exclusive enteral nutrition; washed microbiota transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: NEU-CN-160814