Efficacy and Safety of Fecal Microbiota Transplantation (FMT)

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Intestinal Dysbiosis -A Pilot Study

In recent years, researches illustrate that multifactorial diseases such as functional gastrointestinal disorders, autoimmune diseases, metabolic, behavioral and neurological diseases are associated with an abnormal microbiome structure-dysbiosis, which means the imbalance of the microbiome community. Fecal microbiota transplantation (FMT), the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient aiming to alter the intestine microbiota, is recommended to be performed in Clostridium difficile infection(CDI) as the most effective therapy. It also being used experimentally in the treatment of the disease states linked to dysbiosis of the intestinal microbiota. However, the efficacy and safety of FMT to treat the dysbiosis-associated diseases is still in its infancy. To further verify the indications above, more data is required to be collected through studies.

Study Overview

• Status: Recruiting
• Conditions: Fecal Microbiota Transplantation
• Intervention / Treatment: Procedure: Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yongjian Zhou, MM; Phone Number: 86-13503060150; Email: eyzhouyongjian@scut.edu.cn
• Study Contact Backup: Name: Hongli Huang, MM; Phone Number: 86-13631316718; Email: honglisums@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Recruiting
      • Guangzhou First People's Hospital
      • Contact: Yongjian Zhou, MM; Phone Number: 86-13503060150; Email: eyzhouyongjian@scut.edu.cn
      • Contact: Hongli Huang, MM; Phone Number: 86-13631316718; Email: honglisums@126.com
      • Sub-Investigator: Yandi Liu, MM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Confirmed diagnosis of any of following diseases:

• Irritable Bowel Syndrome
• Ulcerative colitis
• Crohn's disease
• Constipation
• Clostridium Difficile Infection
• Functional Dyspepsia
• Parkinson's Disease
• Metabolic Syndrome
• Non-Alcoholic Fatty Liver Disease
• Autism Spectrum Disorder
• Radiation Enteritis
• Atopic Dermatitis
• Food Allergic
• Graft-versus-Host Disease
• Obesity
• Diabetes mellitus
• Multi-Drug Resistant Infection
• Hepatic Encephalopathy
• Enteric Dysbacteriosis
• Multiple Sclerosis
• Pseudomembranous Enteritis
• Acute Pancreatitis
• Chronic Fatigue Syndrome
• Acute-on-chronic Liver Failure with HBV Infection
• Alcoholic Liver Disease
• Anorexia
• Decompensated Cirrhosis
• Henoch-Schonlein Purpura
• Autoimmune Liver Disease
• Systemic Lupus Erythematosus
• Rheumatoid arthritis
• IgG4-Related Disease
• Celiac Disease
• Protein-losing Enteropathy
• Asperger Syndrome
• Rheumatoid arthritis
• Psoriasis
• Ankylosing spondylitis
• Immune checkpoint inhibition-related colitis
• Autoimmune enteropathy
• Drug-induced diarrhea
• Suffering from gastrointestinal symptoms such as constipation, diarrheas, abdominal pain, flatulence, etc.
• The participants must be able to tolerate the FMT infusion method such as endoscopy, colonoscopy, capsule, nasoduodenal tube insertion, etc.

Exclusion Criteria:

• Current pregnancy or breast-feeding;
• Suffering from other severe diseases, including liver or kidney failure, heart failure, MODS, coma, cerebrovascular accident;
• Known contraindication to all FMT infusion method such as nasoduodenal tube insertion, endoscopy, colonoscopy and enema;
• Any conditions that may render the efficacy of FMT or at the discretion of the investigators.

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

40

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irritable Bowel Syndrome; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Constipation; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Clostridium Difficile Infection; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Functional Dyspepsia; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Parkinson's Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Metabolic Syndrome; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Non-Alcoholic Fatty Liver Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Autism Spectrum Disorder; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Radiation Enteritis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Atopic Dermatitis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Food Allergic; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Graft-versus-Host Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Obesity; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Diabetes mellitus; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Multi-Drug Resistant Infection; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Hepatic Encephalopathy; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Enteric Dysbacteriosis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Multiple Sclerosis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Pseudomembranous Enteritis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Acute Pancreatitis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Chronic Fatigue Syndrome; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Acute-on-chronic Liver Failure with HBV Infection; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Alcoholic Liver Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Anorexia; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Decompensated Cirrhosis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Henoch-Schonlein Purpura; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Autoimmune Liver Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Systemic Lupus Erythematosus; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: IgG4-Related Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Celiac Disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Protein-losing Enteropathy; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Asperger Syndrome; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Rheumatoid arthritis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Ulcerative colitis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Crohn's disease; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Psoriasis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Ankylosing spondylitis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Immune checkpoint inhibition-related colitis; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Autoimmune enteropathy; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation
Experimental: Drug-induced diarrhea; Fecal Microbiota Transplantation will be performed.	Procedure: Fecal Microbiota Transplantation; Procedure: Fecal Microbiota Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of FMT in patients with gastrointestinal symptom will be assessed by the change of Gastrointestinal Symptom Rating Scale(GSRS).	Gastrointestinal Symptom Rating Scale(GSRS) is a measure of gastrointestinal symptom severity in five clusters (pain, bloating, constipation, diarrhea, and early satiety).The items are scored between 1 and 7, where 1 corresponds to "no discomfort at all" and 7 to "very severe discomfort" from the symptom. The participants will be asked to filled in the scale in several time points from baseline to 12 months after FMT.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events(CTCAE) V4.0	1 year

Other Outcome Measures

Outcome Measure	Time Frame
Numbers of patients who have improvement in clinical symptoms (depends on each disease as stated in outcome)	1 year

Collaborators and Investigators

• Sponsor: Guangzhou First People's Hospital
• Investigators: Principal Investigator: Hongli Huang, MM, Guangzhou First People's Hospital

Publications and helpful links

General Publications

• Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30.
• Paramsothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J, Samuel D, Leong RWL, Connor S, Ng W, Paramsothy R, Xuan W, Lin E, Mitchell HM, Borody TJ. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017 Mar 25;389(10075):1218-1228. doi: 10.1016/S0140-6736(17)30182-4. Epub 2017 Feb 15.
• Brandt LJ. American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection. Am J Gastroenterol. 2013 Feb;108(2):177-85. doi: 10.1038/ajg.2012.450. Epub 2013 Jan 15.
• Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. 2017 Apr;17(4):219-232. doi: 10.1038/nri.2017.7. Epub 2017 Mar 6.
• Ooijevaar RE, Terveer EM, Verspaget HW, Kuijper EJ, Keller JJ. Clinical Application and Potential of Fecal Microbiota Transplantation. Annu Rev Med. 2019 Jan 27;70:335-351. doi: 10.1146/annurev-med-111717-122956. Epub 2018 Nov 7.
• Lee P, Yacyshyn BR, Yacyshyn MB. Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT). Diabetes Obes Metab. 2019 Mar;21(3):479-490. doi: 10.1111/dom.13561. Epub 2018 Nov 20.
• Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, Cui C, Shen YQ. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-alpha signaling pathway. Brain Behav Immun. 2018 May;70:48-60. doi: 10.1016/j.bbi.2018.02.005. Epub 2018 Feb 20.
• Johnsen PH, Hilpusch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, Goll R. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):17-24. doi: 10.1016/S2468-1253(17)30338-2. Epub 2017 Nov 1.
• El-Salhy M, Hatlebakk JG, Gilja OH, Brathen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020 May;69(5):859-867. doi: 10.1136/gutjnl-2019-319630. Epub 2019 Dec 18.
• Leshem A, Horesh N, Elinav E. Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome. Front Immunol. 2019 Jun 14;10:1341. doi: 10.3389/fimmu.2019.01341. eCollection 2019.
• DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, Turbett S, Chung RT, Chen YB, Hohmann EL. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019 Nov 21;381(21):2043-2050. doi: 10.1056/NEJMoa1910437. Epub 2019 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: January 10, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: B-2019-041-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No