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Fecal Microbial Transplantation in Patients With Crohn's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03267238
Recruitment Status : Completed
First Posted : August 30, 2017
Last Update Posted : February 21, 2022
Sponsor:
Information provided by (Responsible Party):
Ellen Li, Stony Brook University

Study Description
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Brief Summary:
Fecal Microbiota Transplantation will be offered to eligible Crohn's disease patient as Investigational New Drug treatment

Condition or disease Intervention/treatment Phase
Crohn Disease Biological: Fecal Microbial Transplantation Early Phase 1

Detailed Description:

The following hypothesis will be tested in this study:

  1. Fecal microbiota transplantation is a safe, tolerable procedure.
  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 up to 12 weeks post-transplant in patients with Crohn's disease.

Secondary objectives:

  1. To determine the long term safety and tolerability of fecal microbiota transplantation (FMT) up to one year post transplant in patients with Crohn's disease.
  2. To compare microbial diversity in healthy donor stools compared to pre-FMT recipient stools collected from patients (recipients) with Crohn's disease.
  3. To compare microbial composition in healthy donor stools compared to pre-FMT recipient stools from patients (recipients) with Crohn's disease.
  4. To compare microbial function in healthy donor stools compared to pre-FMT recipient stools from patients (recipients) with Crohn's disease
  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 Crohn's disease.
  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 Crohn's disease.
  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 Crohn's disease.
  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 Crohn's disease.
  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 Crohn's disease.
  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 Crohn's disease.
  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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fecal Microbial Transplantation in Patients With Crohn's Disease
Actual Study Start Date : June 16, 2017
Actual Primary Completion Date : February 15, 2022
Actual Study Completion Date : February 15, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Fecal Microbial transplantation
Fecal Microbial Transplantation will be offered to patients eligible to be part of the study.
 Biological: Fecal Microbial Transplantation
Fecal Microbial Transplantation via will be offered to eligible Crohn's patient
Other Name: FMT


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: 5 years ]
    Number of participants with treatment-related adverse events with grade greater than 2 within one year after FMT will be reported.


Secondary Outcome Measures :
  1. 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. [ Time Frame: 6 years ]
    Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Alpha diversity indices (e.g. Chao1, Shannon complexity H, Shannon Evenness H/Hmax) will be calculated inferred through 1000 replicate resamplings using Explicet. Beta diversity (Bray-Curtis and Jaccard distances) will be calculated for the recipient Pre-FMT, 1 week post-FMT and 12 weeks post-FMT as compared to their pared donor using the adonis function in the R vegan package at the phyla, family and genus level. A linear mixed model will be used to compare alpha-diversity (ShannonH) and beta-diversity (Bray-Curtis and Jaccard distance) between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.

  2. 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. [ Time Frame: 6 years ]
    Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. . Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Linear mixed models analyses on individual OTUs at the genus level will be conducted on 105 OTUs after eliminating OTUs with an average relative abundance of < 0.001% in the donor and recipient pre-FMT samples, and after discarding OTUs where more than 75% of the samples had a zero count. To compare the relative abundance of each OTU between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) will be used by taking the actual counts of each OTU as the outcomes that were assumed to follow a negative binomial distribution. The p-values will be adjusted for multiple comparisons by the Bonferroni correction or by the Benjamin-Hochberg method (FDR < 0.05).

  3. 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. [ Time Frame: 6 years ]
    Fecal DNA samples will undergo shotgun DNA metagenomics sequencing. After removing human sequences, the Reads per kilobase gene length (RKP) will be calculated using HUMANN2 software for individual bacterial proteins/enzymes and pathways. . A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.Linear mixed models analyses on the RPK associated with individual genes and pathways will be analyzed using linear mixed models between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) were used by taking the actual RPK as the outcomes that will be assumed to follow a negative binomial distribution.

  4. To measure the effect of fecal microbial transplantation on microbial function using bacterial metatranscriptomic sequencing [ Time Frame: 6 years ]
    Fecal RNA samples will undergo bacterial metatranscriptomic RNA sequencing. After removing human sequences, the Reads per kilobase transcript (RKP) will be calculated for individual bacterial proteins/enzymes and pathways. A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.

  5. To measure the effect of fecal microbial transplantation on microbial function using targeted metabolomic assays. [ Time Frame: 6 years ]
    Fecal samples will undergo extraction for targeted metabolomics analysis of short chain fatty acids (micrograms/gram stool) using gas chromatography-mass spectrometry, and of bile acids (microgram/gram stool) using liquid chromatography-mass spectrometry. A linear mixed model will be used to compare respectively short chain fatty acid and bile acid metabolites between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.

  6. Determine if FMT causes a statistically significant change in recipient fecal calprotectin levels [ Time Frame: 6 years ]
    Fecal calprotectin (microgram/gram stool) levels will be measured as in the recipient at baseline pre-FMT, 1 week, and 12 weeks post FMT. A linear mixed model will be used to compare fecal calprotectin levels between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for initial Fecal Microbial Transplant for Crohn's disease:

All patients age ≥7 years of age with established diagnosis of Crohn's disease made by a primary gastroenterologist based on history, physical examination, laboratory/radiological studies, and gastrointestinal histology, with one or more of the following criteria:

  1. has been treated with steroid therapy for at least a month
  2. has been treated with immunomodulatory therapy for at least a month
  3. has been treated with biological therapy for at leaset a month

All patients or legal guardians of patients less than 18 years of age will have to give consent. The consent form will outline that although fecal microbiota transplantation appears safe based on past studies, a theoretical risk of transmission of an unrecognized infectious agent or substance exists and could result in an unexpected disease. All patients aged ≥7 and <18 years will have to give assent

Exclusion Criteria:

  1. Patients less than 7 years of age
  2. Scheduled for abdominal surgery within the next 12 weeks
  3. Major abdominal surgery within the past 3 months
  4. Pregnancy (This will be checked through a urine test on the day of procedure)
  5. Anemia: Hemoglobin < 6 g/dL,
  6. Neutropenia: Absolute Neutrophil Count <1500 Both of the above criteria will be checked via screening test or blood test reports within one month prior to the procedure
  7. A known diagnosis of graft vs. host disease
  8. Presence of an intra-abdominal or perianal abscess.
  9. Presence of intestinal cutaneous fistula
  10. Presence of severe intestinal stricture and/or intestinal obstruction
  11. Administration of any investigational drug within the past 2 months
  12. Use of a TNF-α antagonist within 2 weeks of the proposed date of transplantation
  13. Bacteremia within past 4 weeks (28 days)
  14. Severe Crohn's Disease, determined by Pediatric Crohns Disease Activity Index (PCDAI) value of more than 29.
  15. Individuals with severe prior allergic reaction to food;
  16. Individuals with intercurrent illness including but not necessarily limited to: febrile illness, decompensated liver cirrhosis, HIV/AIDS BMT within past 150 days, malignancy, or other severe immunodeficiency.
  17. Individuals at increased risk for complications of endoscopy or procedural sedation (e.g., ASA classification IV and above).
  18. Previous FMT
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267238


Locations
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United States, New York
Stony Brook University Hospital
Stony Brook, New York, United States, 11794
Sponsors and Collaborators
Stony Brook University
Investigators
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Principal Investigator: Ellen Li, MD, PhD Stony Brook University
  Study Documents (Full-Text)

Documents provided by Ellen Li, Stony Brook University:
Study Protocol and Informed Consent Form  [PDF] July 24, 2019

More Information
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Responsible Party: Ellen Li, Professor, Stony Brook University
ClinicalTrials.gov Identifier: NCT03267238    
Other Study ID Numbers: 973349
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: February 21, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plans to share IPD

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
 Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases