Clinical trial NCT03834051: Fecal Microbiota Transplantation for Treatment of Gastrointestinal Dysbiosis or Clearance of ARO
Official title: Prospective, Open-label Trial to Evaluate Efficacy of Fecal Microbiota Transplantation for Treatment of Chronic Gastrointestinal Dysbiosis or Clearance of Antimicrobial Resistant Organism.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Dysbiosis
Antimicrobial Resistant Organism
Lead sponsor: Vancouver Island Health Authority
Sponsor class: OTHER
First posted: 2019-02-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the efficacy of FMTs via rectal administration for 1) symptom improvement in individuals with a formal diagnosis of dysbiosis due to active inflammatory bowel disease or irritable bowel syndrome; 2) clearance of antimicrobial resistant organism from the gastrointestinal tract.

Detailed description: Fecal Microbiota Transplantation (FMT), which had been predominantly utilized by the veterinarians until late 1990's has generated a significant interest for its potential use in various gastrointestinal, psychiatric, neurologic and metabolic disorders within the past few years. Since 2010, there has been an explosion of research, publications and media coverage related to the high efficacy range, 80 - 90% for treatment of recurrent Clostridioides (Clostridium) difficile infection (rCDI). The exact mechanisms of its success in curing CDI are yet to be discovered. Metagenomic studies have shown that patients with rCDI lack protective and diverse colonic microbiome and remain in a state of chronic dysbiosis. Following a successful FMT, the microbiome of a patient with rCDI resembles that of the donor's and remains as such overtime. There is no precise and agreed definition of dysbiosis. For the purpose of this study, dysbiosis is defined as perturbation of host-microbial interactions which results in compositional changes in the fecal microbiota as determined by clinical criteria of constellation of symptoms, including change in the bowel function (diarrhea, constipation or bloating) in which an alteration of the microbiota is either known based on molecular or culture-based profiling or suspected according to the history, which includes but is not limited to repeated or prolonged use of antibiotics or gastrointestinal infection.

The cause of inflammatory bowel dieseases (IBD) is unknown but studies have shown that IBD is a chronic inflammatory disease with altered and decreased microbiota diversity of the gastrointestinal tract when compared to the healthy individuals. Canada has the highest incidence of IBD in the world. The annual total (direct and indirect) health costs is estimated to $2.8 billion or $11,900 per person per year.17 IBD includes Crohn's Disease (CD) and Ulcerative Colitis (UC). While these diseases are collectively referred as IBD, there are distinct differences - most notably the area of the intestinal tract affected and the extent of the inflammation. UC typically affects the colon; the disease usually starts at the anus and may progress upward, and may even involve the entire colon. While in CD, the inflammation tends to occur in patches and may involve any area throughout the entire intestinal tract; however, it most often affects the terminal ileum of the small intestine. Inflammation due to UC involves only the inner intestinal mucosa, while the inflammation in CD disease can extend through the entire thickness of the bowel wall.

The management of CD is challenging due to extra-intestinal manifestations and overlapping symptomology with other inflammatory disorders. Treatment typically targets symptom relief, but and patients' ability to tolerate therapy also plays a key role. UC is characterized by lifelong relapsing and remitting colorectal inflammation. The cause of UC is unknown, but is thought to result from an aberrant immune response to environmental factors in genetically predisposed individuals. Metagenomic studies have shown that both patients with UC and recurrent Clostridiodes difficile infection (rCDI) lack diversity and richness of their colonic microbiota and remain in a state of chronic dysbiosis. While current drug treatments and surgery to remove the colon and rectum can reduce symptoms, they are costly, associated with adverse effects, and do not promote the restoration of healthy gut bacteria. Recent studies have shown that fecal microbiota transplant (FMT) is effective in treating IBD. Recent trials in both CD and UC patients have shown FMT to be an effective therapy to induce and maintain clinical remission.

Microscopic colitis (MC) is a chronic inflammatory disease of the colon as manifested by chronic, watery, non-bloody diarrhea. MC usually occurs in middle-aged individuals with a female preponderance. Currently, there are limited treatment options for MC; budesonide may be effective for short-term treatment of MC and can improve quality of life. However, up to 80% will experience symptomatic relapse following cessation of budesonide. Routine maintenance treatment with budesonide is controversial as long-term treatment may increase the risk of steroid-related side effects.

IBS is characterized by chronic, relapsing abdominal discomfort and altered bowel movements - constipation, diarrhea or mixed (diarrhea and constipation). IBS affects approximately 15-20% of Canadians and its economic and social burden is estimated to be over $6.5 billion per year in healthcare costs, work productivity losses, and reduced quality of life (QoL). The etiology and pathophysiology of IBS are not yet established, but appear to be a complex interplay between the host and environment factors. Currently, there are no evidence-based therapies available to cure IBS. Studies have shown that fecal microbiota transplantation (FMT) may be an effective treatment IBS. Given the lack of safe and effective treatment for IBD and IBS which are thought to be due to gastronintestinal dysbiosis, this study was conducted.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older.
* Able to provide informed consent.
* Willing and able to comply with all the required study procedures.
* Rectally colonized with antimicrobial resistant organisms: Extended-spectrum of beta-lactamase, Carbapenem resistant, vancomycin resistant enterococci

Exclusion Criteria:

* Planned or actively taking another investigational product
* Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
* Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
* Peripheral white blood cell count \> 30.0 x 109/L AND temperature \> 38.0 ºC
* Active gastroenteritis due to Salmonella, Shigella, shiga toxin-producing E. coli, Yersinia or Campylobacter.
* Unable to tolerate FMT or enema for any reason.
* Requiring systemic antibiotic therapy at the time of FMT.
* Actively taking Saccharomyces boulardii or other probiotic; yogurt is allowed
* Severe underlying disease such that the patient is not expected to survive for at least 30 days.
* History of severe allergy to any food

Primary outcomes:
measure: Efficacy of FMT in Active Ulcerative Colitis
timeFrame: 1 year
measure: Efficacy of FMT for Irritable Bowel Syndrome
timeFrame: 1 year
measure: Efficacy of FMT in Crohn's Disease
timeFrame: 4 weeks
measure: Efficacy of FMT in Microscopic Colitis (MC) Based on Physician's Global Assessment
timeFrame: Baseline to 4 weeks following FMT
measure: Efficacy of FMT in Microscopic Colitis (MC) Based on Number of Unformed Bowel Movements in 24 Hours
timeFrame: Baseline to 4 weeks following FMT
Secondary outcomes:
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: Vancouver Island Health Authority
state: British Columbia
Study officials:
affiliation: Vancouver Island Health Authority
name: Christine Lee
role: PRINCIPAL_INVESTIGATOR
References: