Standardized Fecal Microbiota Transplantation for Crohn's Diseases

Efficacy and Safety of Standardized Fecal Microbiota Transplantation for Moderate to Severe Crohn's Diseases

The gut microbiota is considered to constitute a "microbial organ" which has pivotal roles in the intestinal diseases and body's metabolism. Evidence from animal and human studies strongly supports the link between intestinal bacteria and inflammatory bowel diseases (IBD). Dozens of studies reported its efficacy in treatment of severe Clostridium difficile colitis. Preliminary studies using fecal microbiota transplantation (FMT) for Ulcerative Colitis (UC), Crohn's diseases (CD), irritable bowel syndrome (IBS) and constipation have also met with some success. However, the results on CD is very limited. This marks the initial step in exploring the potential efficacy of fecal bacteriotherapy for CD. The investigators aim to evaluate the effectiveness, durability, and safety of FMT in a cohort of at least 500 patients with CD over a ten-year period

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Disease; Crohn's Disease (CD)
• Intervention / Treatment: Procedure: FMT

Detailed Description

The present clinical trial aims to re-establish a gut functionality state of intestinal flora through FMT as a therapy for CD (all age range,HBI>4). We established a standard microbiota isolation from donated fresh stool in lab. The microbiota is then transplanted into the intestine via endoscopy or other established methods, such as mid-gut or colonic transendoscopic enteral tubing. Patients from multi-clinical centers in this study will be assigned to receive FMT or traditional treatments according to associated guidelines and follow-up for at least one year. Blood tests, imaging, endoscopy and questionnaire will be used to assess participants at study start and at study completion.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Faming Zhang, MD, PhD; Phone Number: 86-025-58509883; Email: fzhang@njmu.edu.cn
• Study Contact Backup: Name: Huijie Zhang, MD, PhD; Phone Number: 86-025-58509670; Email: zhjssm@163.com

Study Locations

• China
  • Jiangsu
    • Huai'an, Jiangsu, China, 223000
      • Recruiting
      • The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University
      • Contact: Honggang Wang, MD; Phone Number: 86-18851268720; Email: jgzwhg@njmu.edu.cn
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University
      • Contact: Faming Zhang, MD, PhD; Phone Number: 86-025-58509883; Email: fzhang@njmu.edu.cn
      • Contact: Faming Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Clinical diagnosis of Crohn's disease, with the diagnosis remaining unchanged after at least three months of follow-up.

Willingness to undergo FMT (Fecal Microbiota Transplantation).

Exclusion Criteria:

Presence of serious conditions that made them unsuitable for inclusion (e.g., malignant neoplasms, cardiopulmonary failure, serious liver or kidney disease).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal microbiota transplantation; Standard fecal microbiota transplantation, which has been defined as washed microbiota transplantation since 2019.	Procedure: FMT; Standard FMT
No Intervention: Traditional treatments; Traditional treatments for Crohn's disease and its complications according to the guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Clinical remission defined as HBI score ≦ 4. For patients with complications such as intestinal obstruction, Clinical remission can be defined as obstruction improvement. The endpoint of follow-up is the time of clinical recurrence.	Up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Costs	Social and medical costs	Up to one year
Adverse events	All possible adverse events:fever,abdominal pain,infectious diseases and others	During FMT and ten years after FMT
Sleep quality	evaluated by Pittsburgh Sleep Quality Index (PSQI), with a score range of 0 to 21. Higher PSQI score indicates poorer sleep quality. Insomnia Severity Index (ISI), with a score range of 0 to 28. Higher ISI score indicates more severe insomnia.	before FMT, 1 month after FMT, 12 weeks after FMT
Fatigue	evaluated by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), with a score range of 0 to 52. Higher FACIT-F score indicates lower levels of fatigue and better quality of life.	before FMT, 1 month after FMT, 12 weeks after FMT
Anxiety and depression	evaluated by Hospital Anxiety and Depression Scale (HADS), with a score range of 0 to 42. Higher scores indicate greater severity of anxiety and depression symptoms.	before FMT, 1 month after FMT, 12 weeks after FMT
Symptomatic stricture	evaluated by Crohn's Disease Obstruction Score (CDOS), with a score range of 0 to 6. Higher scores indicate greater severity of obstructive symptoms.	before FMT, 1 month after FMT, 12 weeks after FMT

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Collaborators: Xijing hospital of air force Medical University; The Affiliated Huaian NO.1 People's Hospital of 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.
• Aroniadis OC, Brandt LJ. Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol. 2013 Jan;29(1):79-84. doi: 10.1097/MOG.0b013e32835a4b3e.
• Damman CJ, Miller SI, Surawicz CM, Zisman TL. The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol. 2012 Oct;107(10):1452-9. doi: 10.1038/ajg.2012.93.
• Zhang T, Li P, Wu X, Lu G, Marcella C, Ji X, Ji G, Zhang F. Alterations of Akkermansia muciniphila in the inflammatory bowel disease patients with washed microbiota transplantation. Appl Microbiol Biotechnol. 2020 Dec;104(23):10203-10215. doi: 10.1007/s00253-020-10948-7. Epub 2020 Oct 16.
• Li Q, Ding X, Liu Y, Marcella C, Dai M, Zhang T, Bai J, Xiang L, Wen Q, Cui B, Zhang F. Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease. Front Pharmacol. 2021 May 17;12:658087. doi: 10.3389/fphar.2021.658087. eCollection 2021.
• Xiang L, Ding X, Li Q, Wu X, Dai M, Long C, He Z, Cui B, Zhang F. Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment? Microb Biotechnol. 2020 May;13(3):760-769. doi: 10.1111/1751-7915.13536. Epub 2020 Jan 20.
• Li P, Zhang T, Xiao Y, Tian L, Cui B, Ji G, Liu YY, Zhang F. Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease. Appl Microbiol Biotechnol. 2019 Jan;103(1):349-360. doi: 10.1007/s00253-018-9447-x. Epub 2018 Oct 24.
• Zhang FM, Wang HG, Wang M, Cui BT, Fan ZN, Ji GZ. Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease. World J Gastroenterol. 2013 Nov 7;19(41):7213-6. doi: 10.3748/wjg.v19.i41.7213.
• Zhang T, Xiang J, Cui B, He Z, Li P, Chen H, Xu L, Ji G, Nie Y, Wu K, Fan D, Huang G, Bai J, Zhang F. Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease. Oncotarget. 2017 Oct 4;8(51):88894-88903. doi: 10.18632/oncotarget.21491. eCollection 2017 Oct 24.
• He Z, Li P, Zhu J, Cui B, Xu L, Xiang J, Zhang T, Long C, Huang G, Ji G, Nie Y, Wu K, Fan D, Zhang F. Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn's disease complicated with inflammatory mass. Sci Rep. 2017 Jul 6;7(1):4753. doi: 10.1038/s41598-017-04984-z.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 13, 2013
• First Submitted That Met QC Criteria: February 14, 2013
• First Posted (Estimated): February 18, 2013

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Inflammatory bowel disease; Fecal bacteriotherapy; Fecal microbiota transplantation; Fecal transplantation; Crohn's disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases
• Other Study ID Numbers: FMC-CN-121101