Standardized Fecal Microbiota Transplantation for Ulcerative Colitis

Efficacy, Durability and Safety of Standardized Fecal Microbiota Transplantation in Patients With Moderate to Severe Ulcerative Colitis

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 FMT for Ulcerative Colitis (UC), Crohn's diseases, irritable bowel syndrome (IBS) and constipation have also met with some success. This is an initial step into investigating the potential efficacy of standardized fecal bacteriotherapy through mid-gut (at least below duodenal papilla) for UC, the investigators propose to determine the efficiency and safety of FMT in a series of 500 patients with moderate to severe UC (Montreal classification).

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis; Inflammatory Bowel Disease; Microbiota; Fecal Microbiota Transplantation; Bacteria
• Intervention / Treatment: Procedure: Standardized FMT; Drug: Traditional treatments

Detailed Description

The present clinical trial aims to re-establish a gut functionality state of intestinal microbiota through FMT as a therapy for UC. Investigators established a standard bacteria isolation from donated fresh stool in lab. Then the bacteria is transplanted to mid-gut through regular gastroscope. Patients in this study will assigned to receive FMT(s) or traditional treatments according to associated guidelines and follow-up for long term. All data were recorded in China Microbiota Transplantation System.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Faming Zhang, MD,PhD
• Study Contact Backup: Name: Faming Zhang, MD,PHD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • 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: 086-25-58509883; Email: fzhang@njmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients who had been diagnosed with UC through a combination of typical clinical symptoms, endoscopy, and histological criteria for at least 3 months, and patients who failed to achieve satisfactory efficacy for UC from the previous therapies.

Exclusion Criteria:

Patients were excluded if accompanied by other severe diseases, including other intestinal diseases (e.g., Clostridioides difficile infection), malignant neoplasm, cardiopulmonary failure, and serious liver and kidney disease, refused to complete the follow-up, and underwent FMT or WMT before.

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: Standardized FMT; endoscopy Tubing Once or repeat	Procedure: Standardized FMT; Fecal microbiota transplantation by gastroscopy administration of fresh or frozen bacteria from healthy donor to the mid-gut or whole colon; Other Names: Fecal Microbiota Transplantation; Fecal Microbiota Therapy; fecal transplantation
Experimental: Traditional treatments; Oral Tubing	Drug: Traditional treatments; Medications; Other Names: Traditional treatments according to associated guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of FMT	The efficacy and durability of clinical remission (days) after Fecal Microbiota Transplantation procedure.Defined as Montreal score S0 (clinical remission)	On year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number and severity of adverse events	Ten years
sleep quality evaluated by the Pittsburgh Sleep Quality Index (PSQI)	Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), which consisted of 19 items divided into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.Each component received a value from 0 to 3 and the total scores ranged from 0 to 21, with higher scores indicating poorer sleep quality. Poor sleep quality was defined as total PSQI scores > 5.	before FMT, 1 month and 12 weeks after FMT
sleep quality evaluated by the Insomnia Severity Index (ISI)	Insomnia Severity Index (ISI) was used to evaluate the severity of insomnia, which was composed of 7 items. Each item scored from 0-4, with a total score ranging from 0 to 28. High scores indicated poorer sleep quality. ISI ≥ 8 was set as a subthreshold to clinical insomnia.	before FMT, 1 month and 12 weeks after FMT
anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS)	It had 14 items, 7 each for depression (HADS-D) and anxiety (HADS-A). The total scores ranged from 0 to 21 for HADS-D or HADS-A, with higher score indicating more severe depression or anxiety symptoms. A HADS-A or HADS-D score ≥ 8 was identified as a diagnostic threshold for anxiety or depression in this study.	before FMT, 1 month and 12 weeks after FMT
fatigue evaluated by the Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)	FACIT-F was composed of 13 questions, each with a score of 0-4. Total score ranged from 0 to 52, with lower score suggesting greater fatigue. Fatigue remission was defined as FACIT-F score > 40 after FMT and an increase in the FACIT-F score ≥ 4 indicated fatigue improvement according to the previous study.	before FMT, 1 month and 12 weeks after FMT

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Collaborators: Air Force Military Medical University, China
• Investigators: Study Chair: Huijie Zhang, MD,PhD, The Second Afiliated Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2011 Dec 20;9(2):88-96. doi: 10.1038/nrgastro.2011.244.
• Ding X, Li Q, Li P, Zhang T, Cui B, Ji G, Lu X, Zhang F. Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis. Drug Saf. 2019 Jul;42(7):869-880. doi: 10.1007/s40264-019-00809-2.
• 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.
• Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989 Jan 21;1(8630):164. doi: 10.1016/s0140-6736(89)91183-5. No abstract available.
• Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012 Nov;107(11):1755; author reply p.1755-6. doi: 10.1038/ajg.2012.251. No abstract available.
• 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 K, Marcella C, Liu X, Zhang T, Liu Y, Li P, Xiang L, Cui B, Wang J, Bai J, Zhang F. Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes. Clin Transl Gastroenterol. 2020 Aug;11(8):e00224. doi: 10.14309/ctg.0000000000000224.
• Li Q, Zhang T, Ding X, Xiang L, Cui B, Buch H, Zhang F. Enhancing patient adherence to fecal microbiota transplantation maintains the long-term clinical effects in ulcerative colitis. Eur J Gastroenterol Hepatol. 2020 Aug;32(8):955-962. doi: 10.1097/MEG.0000000000001725.
• Cui B, Li P, Xu L, Zhao Y, Wang H, Peng Z, Xu H, Xiang J, He Z, Zhang T, Nie Y, Wu K, Fan D, Ji G, Zhang F. Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med. 2015 Sep 12;13:298. doi: 10.1186/s12967-015-0646-2.

Helpful Links

• Fecal microbiota transplantation

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 9, 2013
• First Submitted That Met QC Criteria: February 9, 2013
• First Posted (Estimated): February 13, 2013

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Ulcerative colitis; Inflammatory bowel disease; Gut flora; Gut bacteria; Bacteriotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Ulcer; Inflammatory Bowel Diseases; Intestinal Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: FMT-CN-121123