Fecal Microbiota Transplantation (FMT) in the Management of Ulcerative Colitis (UC)

Ulcerative Colitis Clinical Trial

Official title:

Fecal Microbiota Transplantation (FMT) in the Management of Ulcerative Colitis (UC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02516384
• Other study ID #: 1404014982
• Status: Completed
• Phase: Phase 1
• First received: July 29, 2015
• Last updated: February 20, 2018
• Start date: October 1, 2016
• Est. completion date: January 31, 2017

Study information

• Verified date: February 2018
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Inflammatory bowel disease is a condition caused by gastrointestinal immune system dysregulation and affected by both genetic and environmental factors. Differences in intestinal bacteria exist between IBD patients and healthy controls, but the role of intestinal bacteria in the development and treatment of IBD remains largely unknown. Fecal microbiota transplantation (FMT) is the transfer of gastrointestinal bacteria from a healthy donor to a patient with altered microbial diversity with the intent of restoring a normal bacterial balance. Most studies focus on its use in treating Clostridium difficile (CDI), an infection characterized by dysbiosis. Given the role of dysbiosis in IBD, the investigators hypothesize that FMT may be beneficial in IBD. The purpose of this study is to prospectively examine the safety of FMT in the management of ulcerative colitis (UC).

Description:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with significant morbidity and mortality. Current therapies remain limited by side effects and loss of response over time, and there is an ongoing need for new therapies. Fecal microbiota transplantation (FMT), which has proven to be safe and effective in the management of Clostridium difficile infection (CDI) has been proposed as a therapy for UC. There have been studies examining the role of FMT in UC, but they have shown mixed results, and have not examined the underlying immunologic and microbial changes to explain how and why FMT works from specific donors and in certain recipients. Furthermore, no studies have examined the long-term safety of FMT in patients with UC. This proposal aims to examine: (a) the short- and long-term safety of FMT in patients with UC, (b) the efficacy of FMT as a therapy for mild-moderate UC, and (c) the microbial and immunologic changes that occur after FMT, to help understand how and why it works in this group of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 31, 2017
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with biopsy proven ulcerative colitis (UC), including those with inadequately controlled UC (flare) as defined by failure of standard medical therapy, steroid-dependence, and/or need for escalation of medical care as determined by severity index (Mayo Score), endoscopic or histologic study, and/or medical provider

• Have active disease, defined with a Mayo Score > 3 and Mayo endoscopic subscore >1

• Subjects whom the investigator believes can and will comply with the requirements of the protocol

• Able to provide informed written consent.

Exclusion Criteria:

• Biopsy-proven Crohn's disease or indeterminate colitis

• Acute abdomen or other clinical emergencies requiring emergent management (for example: stricture, bowel obstruction, perforation and/or abscess)

• Primary sclerosing cholangitis (PSC)

• Pregnancy

• Concurrent Clostridium difficile infection or other known infection

• Prior history of fecal microbiota transplantation

• Other causes of diarrhea, including but not limited to tube feeds and medications (for example, kayaxelate, metformin, lactulose, laxatives, magnesium)

• Major congenital defects

• Subjects with recent malignancy in the last 5 years, excluding non-melanoma skin malignancies

• Anaphylactic reactions to any foods

• Any antibiotic use within the last 3 months

• Subject having any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant participating in the study, would make it unlikely for the participant to complete the study, or would confound the study

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• Fecal Microbiota Transplantation
We will use fecal microbiota transplantation (FMT), with fecal material obtained from OpenBiome or donor directed, to assess safety (as primary outcome) and efficacy (as secondary outcome) in adult (>18 year old) patients with active ulcerative colitis (UC).

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (14)

Angelberger S LC, Gratzer C, al. e. Fecal transplantation in patients with moderately to severely chronic active ulcerative colitis (UC). ECCO Conference Abstracts 2012:P374

Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989 Jan 21;1(8630):164. — View Citation

Borody TJ, Campbell J. Fecal microbiota transplantation: techniques, applications, and issues. Gastroenterol Clin North Am. 2012 Dec;41(4):781-803. doi: 10.1016/j.gtc.2012.08.008. Review. — View Citation

Brandt L AO, Greenberg A, et al. Safety of Fecal Microbiota Transplantation (FMT) in Immunocompromised (Ic) Patients with Inflammatory Bowel Disease (IBD). Am J Gastroenterol 2013, 108:S556.

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. Review. — View Citation

Greenberg A AO, Shelton C, Brandt L. Long-term Follow-up Study of Fecal Microbiota Transplantation (FMT) for Inflammatory Bowel Disease (IBD). Am J Gastroenterol 2013, 108:S540.

Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006 Jan;12 Suppl 1:S3-9. Review. — View Citation

Kump PK, Gröchenig HP, Lackner S, Trajanoski S, Reicht G, Hoffmann KM, Deutschmann A, Wenzl HH, Petritsch W, Krejs GJ, Gorkiewicz G, Högenauer C. Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis. 2013 Sep;19(10):2155-65. doi: 10.1097/MIB.0b013e31829ea325. — View Citation

Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr, Cloney D, Kugathasan S. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):597-601. doi: 10.1097/MPG.0b013e318292fa0d. — View Citation

Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004 May;126(6):1504-17. — View Citation

Nagalingam NA, Lynch SV. Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2012 May;18(5):968-84. doi: 10.1002/ibd.21866. Epub 2011 Sep 20. Review. — View Citation

Sartor RB, Muehlbauer M. Microbial host interactions in IBD: implications for pathogenesis and therapy. Curr Gastroenterol Rep. 2007 Dec;9(6):497-507. Review. — View Citation

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16. — View Citation

Vermeire S JM, Verbeke K, al e. Pilot study on the safety and efficacy of faecal microbiota transplantation in refractory crohn's disease. Gastroenterology 2012, 142:S360.

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety post-FMT as determined by interview for adverse events	Patient information regarding adverse events and safety of FMT for UC will be collected throughout the study period, including day 0, weeks 1, 2, 4, 6, 12 24, and then every 6 months until 36 months post-FMT. Throughout the study period, patients will be assessed for safety with questions regarding general well-being (such as "how have you been feeling?"), as well as specific questions to evaluate for occurrence of adverse events. Patients will also be questioned regarding stool form and frequency, presence of abdominal pain, fevers and subjective well-being.	36 months post-FMT
Secondary	Clinical remission	Defined by Mayo score = 2 without any subscore >1, and Mayo endoscopic subscore 0-1	2, 4 and 12 weeks post fecal microbiota transplantation
Secondary	Clinical Response	Defined by decrease in Mayo score by 3 points, decrease in bleeding subscore by 1, or absolute subscore of 0-1	2, 4 and 12 weeks post fecal microbiota transplantation
Secondary	Progression of disease defined by initiation of anti-TNF agents	Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab), vedolizumab, steroids. Includes time gap until additional agents are started	2, 4 and 12 weeks post fecal microbiota transplantation
Secondary	Progression of disease defined by increase in dosages of current UC medications	Increase in dosages of current ulcerative colitis specific medications	2, 4 and 12 weeks post fecal microbiota transplantation
Secondary	Progression of disease defined by time to colectomy	Time to colectomy rates and increase in time to colectomy	up to three year follow-up period post fecal microbiota transplantation
Secondary	Death secondary to UC	Time to death secondary to ulcerative colitis	Anytime during the three year follow-up period post fecal microbiota transplantation
Secondary	Progression of disease defined by clinical flare	Time to next flare	2, 4 and 12 weeks post fecal microbiota transplantation
Secondary	Microbial changes	- Alterations in microbial profiles as defined by sequence of genetic material from fecal material.	0, 2 and 4 weeks post fecal microbiota transplantation
Secondary	Immunological changes	- Alterations in immune cell function as defined by RNA sequencing and flow cytometry	0, 2 and 4 weeks post fecal microbiota transplantation