Efficacy of Fecal Microbiota Transplantation for Inflammatory Bowel Disease

Ulcerative Colitis Clinical Trial

Official title:

Efficacy of Fecal Microbiota Transplantation for Refractory Inflammatory Bowel Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02575040
• Other study ID #: GMMA-Fecal Tx-1
• Status: Recruiting
• Phase: Phase 3
• First received: October 6, 2015
• Last updated: October 12, 2015
• Start date: May 2015
• Est. completion date: May 2020

Study information

• Verified date: October 2015
• Source: Gulhane Military Medical Academy
• Contact: Hakan Demirci, M.D.
• Phone: 00905325140028
• Email: hakandemircigata[@]yahoo.com
• Is FDA regulated: No
• Health authority: Turkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The gut microbiota is determined 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 flora and inflammatory bowel diseases. Lots of studies showed its efficacy in treatment of severe Clostridium difficile colitis. Corticosteroid dependence in patients with ulcerative colitis (UC) and Crohn's disease (CD) is an important clinical problem and maintenance of steroid-free remission is a key treatment goal. Early studies using fecal microbiota transplantation (FMT) for Ulcerative Colitis (UC) and Crohn's diseases have also met with success. This is an first step into investigating the potential efficacy of standardized FMT through terminal ileum for UC and CD, the investigators propose to determine the efficiency and safety of FMT in a series of 80 patients with moderate to severe UC and CD.

Description:

Intestinal microbiota have a major role in disease pathogenesis, either in a form of a "permissive" role or as a direct pathogenic cause.

Clostridium difficile colitis; irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) have all been connected to a disturbance in the equilibrium of intestinal microbiome. The cause of IBD in unknown but evidence is getting that immense immune reaction of intestinal immune system to microflora combined with a genetic predisposition are responsible for the chronic inflammation.

Fecal microbial treatment (FMT) is a treatment that utilizes the microbiota of a healthy intestine as a probiotic preparation. The fecal material of a healthy individual is fluidized and that inserted into the intestinal tract of a sick individual, assuming that the healthy flora will colonize and cure the intestine. Previous work had shown success in fecal transplantation as a treatment for clostridium difficile colitis. There are also reports of the efficacy of this treatment for inflammatory bowel disease but currently the numbers are small. 41 cases were reported , In some the FMT was inserted through a nasogastric tube directly to the duodenum, in some be colonoscopy and in some by an enema. A significant clinical improvement was reported in 19 of 25 patients. 13 of 17 stopped IBD treatment , 15 of 24 entered full clinical remission. In all 15 patients treated for infection the treatment was successful. No sever adverse effects were reported, Fever was developed in 8 cases and in one case there was exacerbation of colitis after treatment.

Primary aim: To investigate whether use of FMT will bring improvement of at least 2 points in partial mayo score in ulcerative colitis patients, or 75 points in CDAI of patients with Crohn's colitis. One month after FMT.

Improvement will be defined as:

For Ulcerative colitis: a decrease of at least 2 points in the partial mayo score, and a decrease of at least 1 point in endoscopic Mayo score.

For Crohn's disease: A decrease of at least 70 points in Crohn's disease activity index (CDAI).

80 patients aged >18 years, with histological and endoscopic diagnosis of ulcerative colitis (UC) or CD who did not respond to either thiopurines or tumor necrosis factor (TNF) inhibitors.

Flare will be defined as partial mayo score higher then 3, with either C reactive protein (CRP) higher than 6 or endoscopic mayo score >1 in ulcerative colitis and CDAI higher them 220 and CRP higher than 6 in Crohn's colitis.

Stool will be donated by the patients choice either from a relative, preferably a partner to minimize possible transference of an infective agent, alternatively samples will be ordered from "open biom".

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2020
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent

• Inflammatory bowel disease diagnosed at least 6 months ago

• Failure of either one immunomodulator of at least 3 months duration, or TNF inhibitor full induction treatment, or corticosteroids, or intolerance to either of these drugs.

• Currently active disease, partial Mayo score =4 for ulcerative colitis, or CDAI =200 for CD.

• negative HIV , Human T-cell leukemia virus I/II, negative stool culture, Negative C diff toxin, negative Cytomegalovirus

Exclusion Criteria:

• No informed consent

• Non active inflammatory bowel disease.

• Active infection in either the donor or the recipient,

• Response to biological agents

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Constipation
• Constipation (Excl Faecal Impaction)
• Crohn Disease
• Fecal Impaction
• Inflammatory Bowel Diseases
• Ulcerative Colitis

Intervention

Biological:
• Fecal microbiota transplantation
Fecal microbiota transplantation to patients with ulcerative colitis and Crohn disease

Locations

Country	Name	City	State
Turkey	Gulhane Military Medical Academy	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Gulhane Military Medical Academy

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

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: 1 — View Citation

Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol. 2015 May 7;21(17):5359-71. doi: 10.3748/wjg.v21.i17. — View Citation

Wei Y, Zhu W, Gong J, Guo D, Gu L, Li N, Li J. Fecal Microbiota Transplantation Improves the Quality of Life in Patients with Inflammatory Bowel Disease. Gastroenterol Res Pract. 2015;2015:517597. doi: 10.1155/2015/517597. Epub 2015 Jun 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients with worsened disease	Number of patients with worsened disease. Increase in Montreal score S1, S2 and S3.	one year	Yes
Primary	Adverse events	Number of adverse events	one year	Yes