Safety and Efficacy of Fecal Microbiota Transplantation

Safety and Efficacy of Fecal Microbiota Transplantation: A Pilot Study

The gut microbiota is critical to health and functions with a level of complexity comparable to that of an organ system. Dysbiosis, or alterations of this gut microbiota ecology, have been implicated in a number of disease states. Fecal microbiota transplantation (FMT), defined as infusion of feces from healthy donors to affected subjects, is a method to restore a balanced gut microbiota and has attracted great interest in recent years due to its efficacy and ease of use. FMT is now recommended as the most effective therapy for CDI not responding to standard therapies.

Recent studies have suggested that dysbiosis is associated with a variety of disorders, and that FMT could be a useful treatment. Randomized controlled trial has been conducted in a number of disorders and shown positive results, including alcoholic hepatitis, Crohn's disease (CD), ulcerative colitis (UC), pouchitis, irritable bowel syndrome (IBS), hepatic encephalopathy and metabolic syndrome. Case series/reports and pilot studies has shown positive results in other disorders including Celiac disease, functional dyspepsia, constipation, metabolic syndrome such as diabetes mellitus, multidrug-resistant, hepatic encephalopathy, multiple sclerosis, pseudo-obstruction, carbapenem-resistant Enterobacteriaceae (CRE) or Vancomycin-resistant Enterococci (VRE) infection, radiation-induced toxicity, multiple organ dysfunction, dysbiotic bowel syndrome, MRSA enteritis, Pseudomembranous enteritis, idiopathic thrombocytopenic purpura (ITP), and atopy.

Despite FMT appears to be relatively safe and efficacious in treating a wide range of disease, its safety and efficacy in a usual clinical setting is unknown. More data is required to confirm safety and efficacy of FMT. Therefore, the investigators aim to conduct a pilot study to investigate the efficacy and safety of FMT in a variety of dysbiosis-associated disorder.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Dependence; Multiple Sclerosis; Obesity; Diabetes Mellitus; Hepatic Encephalopathy; Irritable Bowel Syndrome; Constipation; Celiac Disease; Crohn Disease; Ulcerative Colitis; Liver Disease; Idiopathic Thrombocytopenic Purpura; Clostridium Difficile Infection; Alopecia; Autism; Multiple Organ Dysfunction Syndrome; Functional Dysphonia; Graft-versus-host Disease; Carbapenem-Resistant Enterobacteriaceae Infection; Multidrug -Resistant Infection; Pseudo-Obstruction; Vancomycin Resistant Enterococci Infection; Dysbiotic Bowel Syndrome; MRSA Enteritis; Pseudomembranous Enterocolitis; Atopy or Allergy; Psoriatic Arthropathy
• Intervention / Treatment: Procedure: Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthew Fung; Phone Number: +852 35053855; Email: mfung@cuhk.edu.hk

Study Locations

• Hong Kong
  • Shatin
    • Hong Kong, Shatin, Hong Kong, 000000
      • Recruiting
      • The Chinese University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Confirmed diagnosis of any of the following diseases:

• Crohn's disease
• Ulcerative colitis
• Celiac disease
• Irritable bowel syndrome
• Functional dyspepsia
• Constipation
• Antibiotic-associated diarrhea or any antibiotic- associated complications/symptoms
• Metabolic syndrome such as diabetes mellitus and obesity
• Multidrug-resistant infection
• Hepatic encephalopathy
• Multiple sclerosis
• Pseudo-obstruction
• Carbapenem-resistant Enterobacteriaceae (CRE) or Vancomycin-resistant Enterococci (VRE) infection
• Multiple organ dysfunction
• Dysbiotic bowel syndrome
• MRSA enteritis
• Pseudomembranous enteritis
• Alopecia, autism
• Graft-versus-host disease
• Idiopathic thrombocytopenic purpura (ITP)
• Atopy or allergy
• Liver disease such as Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH)
• Alcohol dependence
• Psoriatic arthropathy that has suboptimal control of disease despite standard treatment.

Exclusion Criteria:

• Known contraindication to all FMT infusion method such as nasoduodenal tube insertion, oesophago-gastro-duodenoscopy (OGD), enteroscopy, colonoscopy and enema
• Any conditions that may render the efficacy of FMT or at the discretion of the investigators
• Current pregnancy

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

25

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crohn's disease; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Ulcerative colitis; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Celiac disease; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Irritable bowel syndrome; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Functional dyspepsia; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Constipation; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Metabolic disease (diabetes mellitus or obesity); Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Multidrug-resistant infection; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Hepatic encephalopathy; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Multiple sclerosis; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Pseudo-obstruction; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: CRE infection; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: VRE infection; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Multiple organ dysfunction; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Dysbiotic bowel syndrome; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: MRSA enteritis; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Pseudomembranous enteritis; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Alopecia; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Autism; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Graft-versus-host disease; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Idiopathic thrombocytopenic purpura; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Atopy or allergy; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Liver disease; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Alcohol dependence; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation
Experimental: Antibiotic-associated diarrhea; Fecal Microbiota Transplant will be performed.	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The efficacy of FMT in treating dysbiosis-associated disorder will be assessed by number of patients who have improvement in clinical symptoms (depends on each disease as stated in outcome)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	1 year

Other Outcome Measures

Outcome Measure	Time Frame
Any improvement or deterioration or recurrence of the underlying condition by clinical judgement of doctors	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Siew Ng, Chinese University of Hong Kong

Publications and helpful links

General Publications

• Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015 Jul;149(1):110-118.e4. doi: 10.1053/j.gastro.2015.03.045. Epub 2015 Mar 30.
• Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.
• 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.
• Philips CA, Pande A, Shasthry SM, Jamwal KD, Khillan V, Chandel SS, Kumar G, Sharma MK, Maiwall R, Jindal A, Choudhary A, Hussain MS, Sharma S, Sarin SK. Healthy Donor Fecal Microbiota Transplantation in Steroid-Ineligible Severe Alcoholic Hepatitis: A Pilot Study. Clin Gastroenterol Hepatol. 2017 Apr;15(4):600-602. doi: 10.1016/j.cgh.2016.10.029. Epub 2016 Nov 2. No abstract available.
• Yang Z, Wang X, Bu C. Fecal microbiota transplant for Crohn's disease: a prospective, randomized study in chinese population. United european gastroenterology journal. Conference: 25th united european gastroenterology week, UEG 2017. Spain. Volume 5, 2017:A112-a113
• Costello SP, Waters O, Bryant RV, et al. Short duration, low intensity, pooled fecal microbiota transplantation induces remission in patients with mildmoderately active ulcerative colitis: A randomised controlled trial. Gastroenterology 2017;152 (5 Supplement 1):S198-S199
• Kirk KF, Kousgaard SJ, Nielsen HL, et al. Faecal transplant for the treatment of chronic pouchitis-A randomised, placebo-controlled, clinical trial. Colorectal Disease 2017;19 (Supplement 2):143
• Johnsen PH, Hilpusch F, Cavanagh JP, et al. Fecal transplantation in Irritable Bowel Syndrome (IBS): An RCT. Neurogastroenterology and Motility 2017;29 (Supplement 2):135.
• Holster S, Repsilber D, Brummer RJ, et al. Faecal microbiota transfer in irritable bowel syndrome-clinical outcomes of a randomised placebo-controlled trial. United European Gastroenterology Journal 2017;5 (5 Supplement 1):A155-A156.
• Holster S, Brummer RJ, Repsilber D, et al. Fecal microbiota transplantation in irritable bowel syndrome and a randomized placebo-controlled trial. Gastroenterology 2017;152 (5 Supplement 1):S101-S102.
• Holger Johnsen P, Mazzawi T, El-Salhy M, et al. Effect of faecal microbiota transplantation on the enteroendocrine cells of the colon in patients with Irritable Bowel Syndrome (IBS): Double blinded-placebo controlled study. Neurogastroenterology and Motility 2017;29 (Supplement 2):71.
• Bajaj JS, Kassam Z, Fagan A, et al. Fecal microbiota transplant using a precision medicine approach is safe, Associated with lower hospitalization risk and improved cognitive function in recurrent hepatic encephalopathy. Journal of Hepatology 2017;66:S49-S49.
• Mullish BH, McDonald JAK, Thursz MR, Marchesi JR. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Oct;66(4):1354-1355. doi: 10.1002/hep.29369. Epub 2017 Aug 26. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Estimated): October 31, 2023
• Study Completion (Estimated): October 31, 2030

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Skin Diseases; Respiratory Tract Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Disease Attributes; Disease; Hematologic Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Hemorrhage; Hemorrhagic Disorders; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Arthritis; Otorhinolaryngologic Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Shock; Pathological Conditions, Anatomical; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Malabsorption Syndromes; Inflammatory Bowel Diseases; Brain Diseases, Metabolic; Spondylarthropathies; Spondylarthritis; Spondylitis; Thrombotic Microangiopathies; Psoriasis; Laryngeal Diseases; Hypotrichosis; Hair Diseases; Voice Disorders; Liver Diseases; Alcoholism; Multiple Sclerosis; Syndrome; Irritable Bowel Syndrome; Infections; Communicable Diseases; Purpura; Purpura, Thrombocytopenic; Celiac Disease; Crohn Disease; Enterocolitis; Hepatic Encephalopathy; Brain Diseases; Arthritis, Psoriatic; Constipation; Enteritis; Purpura, Thrombocytopenic, Idiopathic; Clostridium Infections; Enterocolitis, Pseudomembranous; Graft vs Host Disease; Alopecia; Multiple Organ Failure; Dysphonia; Enterobacteriaceae Infections
• Other Study ID Numbers: FMT-Pilot

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