Clinical trial NCT03268213: Fecal Microbial Transplantation for C. Difficile and/or Ulcerative Colitis or Indeterminate Colitis
Official title: Fecal Microbial Transplantation in Patients With Medication Refractory Clostridium Difficile and/or Ulcerative Colitis or Indeterminate Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Clostridium Difficile Infection
Ulcerative Colitis
Indeterminate Colitis
Lead sponsor: Stony Brook University
Sponsor class: OTHER
First posted: 2017-08-31
Enrollment: 12
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: FMT is offered as a treatment to eligible patients
Primary purpose: TREATMENT

Brief summary: Fecal Microbiota Transplantation will be offered to eligible C. difficile patients (does not require Investigational New Drug designation) and to eligible ulcerative colitis or indeterminate colitis patients as Investigational New Drug treatment

Detailed description: The following hypothesis will be tested in this study:

1. Fecal microbiota transplantation is a safe, tolerable, and efficacious procedure for C. difficile patients and is a safe and tolerable procedure for ulcerative colitis and indeterminate colitis patients.
2. The fecal microbial diversity, composition and function in stool recipients after fecal transplantation will change to a similar microbial diversity, composition and functionality as found in donor stool.

Primary objectives:

1. To determine the short term safety and tolerability of fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis up to 12 weeks post-transplant.

Secondary objectives:

1a. To determine the long term safety and tolerability of fecal microbiota transplantation up to 1 year post-transplant in patients with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

1b. To determine the efficacy of fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile defined as no recurrence of C. difficile within one year.

2. To compare microbial diversity in healthy donor stools compared to pre-FMT recipient stools collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

3. To compare microbial composition in healthy donor stools compared to pre-FMT recipient stools from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

4. To compare microbial function in healthy donor stools compared to pre-FMT recipient stools from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

5. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with 1 week post-transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

6. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with 1 week post-transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

7. To compare microbial function in healthy donor stools and pre-FMT recipient stools with 1 week post-transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

8. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with 12 week post transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

9. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with 12 week post transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

10. To compare microbial function in healthy donor stools and pre-FMT recipient stools with 12 week post transplant recipient stool samples collected from patients (recipients) with recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or indeterminate colitis.

11. Stool calprotectin levels will be measured in the recipient at baseline pre-FMT, 1 week and 12 weeks post FMT to determine if FMT causes a statistically significant change.

Eligibility criteria: For C. difficile patients/recipients only:

Inclusion:

1. Patient is 7 years of age or older. 2. One of the following: 2a. At least two recurrences (total three CDI infections) of mild to moderate C. difficile (\<6 diarrheal stools/day) diagnosed by positive toxin PCR or EIA after completing standard medical therapy with metronidazole, vancomycin or fidaxomicin.

2b. At least two episodes of severe C. difficile infection (\>6 diarrheal stools/day requiring hospitalization and associated with significant morbidity).

2c. Moderate C. difficile infection (3-6 diarrheal stools/day not responding to successive standard therapy, e.g. metronidazole, vancomycin and/or fidaxomicin) lasting at least 28 days.

2d. Severe and/or fulminant C. difficile colitis (\> 6 diarrheal stools/day) with no response to standard therapy after 48 hours.

Exclusion:

1. younger than 7 year old
2. scheduled for abdominal surgery within the next 12 weeks
3. had major abdominal surgery within the past 3 months
4. pregnancy
5. Hemoglobin \< 6 g/dL
6. absolute neutrophil count less than 1500/mm3
7. known diagnosis of graft vs. host disease
8. used an investigational drug within the past 2 months
9. used a TNFα agonist within the past 2 weeks
10. diagnosed with Bacteremia within the past 4 weeks

For patients with ulcerative and indeterminate colitis only:

Inclusion:

1. Patient is 7 years of age or older.
2. One of the following:

2a. treated with steroid therapy for at least one month. 2b. treated with immunomodulatory therapy for at least one month 2c. treated with biological therapy for at least one month.

Exclusion:

1. younger than 7 years old
2. scheduled for abdominal surgery within the next 12 weeks
3. had major abdominal surgery within the past 3 months
4. pregnancy
5. Hemoglobin \< 6 g/dL
6. absolute neutrophil count less than 1500/mm3
7. known diagnosis of graft vs. host disease
8. used an investigational drug within the past 2 months
9. used a TNFα agonist within the past 2 weeks
10. diagnosed with Bacteremia within the past 4 weeks
11. previous FMT

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 9 years
Secondary outcomes:
measure: To measure the effect of fecal microbial transplantation on microbial diversity in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
timeFrame: 10 years
measure: To measure the effect of fecal microbial transplantation on microbial composition in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
timeFrame: 10 years
measure: To measure the effect of fecal microbial transplantation on microbial function using shotgun DNA metagenomic in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
timeFrame: 10 years
measure: To measure the effect of fecal microbial transplantation on microbial function using bacterial metatranscriptomic sequencing
timeFrame: 10 years
measure: To measure the effect of fecal microbial transplantation on microbial function using targeted metabolomic assays.
timeFrame: 10 years
measure: Determine if FMT causes a statistically significant change in recipient fecal calprotectin levels
timeFrame: 10 years
measure: Determine number of C. difficile recipients who have recurrent C. difficile within a year after fecal microbial transplant
timeFrame: 10 years
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
Study officials:
affiliation: Stony Brook Medicine
name: Anupama Chawla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mintz M, Khair S, Grewal S, LaComb JF, Park J, Channer B, Rajapakse R, Bucobo JC, Buscaglia JM, Monzur F, Chawla A, Yang J, Robertson CE, Frank DN, Li E. Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis. PLoS One. 2018 Jan 31;13(1):e0190997. doi: 10.1371/journal.pone.0190997. eCollection 2018.