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FMT for MDRO Colonization After Infection in Renal Transplant Recipients (PREMIX)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02922816
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : July 18, 2019
Information provided by (Responsible Party):
Colleen S Kraft, MD, MSc, Emory University

Brief Summary:

Transplant patients are at increased risk of colonization and infection with Multidrug Resistant Organisms (MDROs) due to medications that modify their immune systems, increased healthcare and antibiotic exposure, and surgical manipulation of mucosa. In this study, kidney transplant patients who have infections with resistant bacteria will be given a Fecal Microbiota Transplant (FMT), also known as a fecal transplant, after they receive antibiotic treatment. This study will see if FMT will eliminate the resistant bacteria so that the kidney transplant patients do not have to use last resort antibiotics.

This Phase 1 pilot study is to obtain preliminary safety data for FMT in renal transplant patients to support the rationale for a subsequent clinical trial, not to establish efficacy or toxicity. This trial is designed to test the safety of FMT, identify clinical outcomes, assess feasibility, and refine the target population in participants with MDRO colonization and intestinal dysbiosis. Data from this study should provide directions for the design of future clinical trials.

Condition or disease Intervention/treatment Phase
Infection Due to Resistant Organism Biological: Fecal Microbiota Transplant (FMT) Procedure: Bowel preparation Procedure: Stool or perirectal swab sampling Other: Fasting Phase 1

Detailed Description:

Potential participants who meet key eligibility criteria [adults who have undergone renal transplantation and have a history of infection with the Target Multidrug Resistant Organisms (MDRO)] will be approached for consideration of study participation. For this study, Target MDRO colonization is defined as a positive bacterial culture of either carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus (VRE), Extended Spectrum Beta-Lactamases (ESBL), and/or multidrug resistant (MDR) Pseudomonas from stool or perirectal swab sampling.

The 20 trial participants will be randomized in a 1:1 ratio to one of two arms: the control arm [not receiving Allogeneic Human Stool in Glycerol (10%; AHSG) via Fecal Microbiota Transplant (FMT)] and the experimental arm (receiving AHSG via FMT). Participants in the control arm participants can crossover to receive the treatment after completing a study cycle without FMT. Each cycle lasts 6 weeks and participants will complete a maximum of 2 treatment cycles; participants randomized to the experimental arm will complete a maximum of two cycles and those randomized to the control arm will complete up to three cycles. Upon completion of the final cycle, all trial participants will be followed for just over 6 months.

In addition to the trial participants, there will also be one stool donor participant. The consented, screened, and eligible stool donor will be identified from an established group of stool donors and will undergo screening procedures that are specific to this study. This individual will donate human stool for the preparation of the AHSG (known as the investigational new drug (IND) product for this study). Upon processing of AHSG, the stool donor will enter the Follow-Up Period and remain available for communication to the study team (if necessary) until the Study Completion Date. However, no scheduled study assessments are required of the stool donor.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Using Fecal Microbiota Transplant in Renal Transplant Recipients to Eliminate Multidrug-Resistant Organism Colonization After Infection and Compare Gastrointestinal Carriage in a Randomized, Controlled, Crossover Design
Actual Study Start Date : December 1, 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Control arm
The control arm will participate in the bowel preparation and stool or perirectal swab sampling but will not receive Fecal Microbiota Transplant (FMT) nor will they be fasting during their first study cycle (Cycle 0). Participants testing positive for a multi-drug resistant organism at the of Cycle 0 will be eligible to receive microbiota restoration transplant (MRT) for up to two cycles, as necessary (Cycles 1 and 2).
Procedure: Bowel preparation
Trial participants will undergo the bowel preparation by taking magnesium citrate the day before the cycle begins (Day -1).

Procedure: Stool or perirectal swab sampling
Stool or perirectal swabs will be collected at screening (for eligibility determination) and Days 1, 2, 15, and 36 of each cycle.

Experimental: Fecal Microbiota Transplant (FMT)
The experimental arm will participate in the bowel preparation, stool or perirectal swab sampling, and will receive Fecal Microbiota Transplant (FMT) using Allogeneic Human Stool in Glycerol 10% (AHSG) on Day 1 of each cycle (Cycles 1 and 2).
Biological: Fecal Microbiota Transplant (FMT)
The Fecal Microbiota Transplant (FMT) using Allogeneic human stool in glycerol (10%) (AHSG) intervention will be administered via rectal retention enema and performed in either an inpatient or outpatient clinic.

Procedure: Bowel preparation
Trial participants will undergo the bowel preparation by taking magnesium citrate the day before the cycle begins (Day -1).

Procedure: Stool or perirectal swab sampling
Stool or perirectal swabs will be collected at screening (for eligibility determination) and Days 1, 2, 15, and 36 of each cycle.

Other: Fasting
In Cycle 1 and Cycle 2, participants cannot consume food, alcohol, or other liquids on Day 1 prior to the intervention. Trial participants will not be fasting on Day 1 of Cycle 0.

Primary Outcome Measures :
  1. The safety and feasibility of using FMT in adult participants with Target MDRO colonization after infection will be measured by comparing the number of adverse events (assessed by CTCAE v4.0) after Day 1 of each cycle as compared to baseline. [ Time Frame: Up to 30 weeks ]

Secondary Outcome Measures :
  1. Determine the rate of Target MDRO colonization between the control and experimental arms at screening and on Day 36 of each cycle. [ Time Frame: Up to 30 weeks ]

Other Outcome Measures:
  1. Change in diversity measures of microbiota profile using 16S Image result for recombinant DNA (rDNA). [ Time Frame: Up to 30 weeks; Day 1, Day 15 and Day 36 of each cycle ]
    If participants consent to an optional sub-study, urine pharmacokinetics, blood pharmacokinetics, and blood biomarkers will be drawn.

  2. Assess microbiota changes between the donor and trial participants [ Time Frame: Up to 30 weeks; Day 1, Day 15 and Day 36 of each cycle ]

    Results of the stool or perirectal swab cultures obtained at the screening visit will be compared with the culture results from samples collected on Days 1, 15, and 36 of each cycle to characterize the genomic relatedness and microbiota changes between the donor and trial participants using 16S ribosomal RNA (rRNA) sequencing.

    16S is a common amplicon sequencing method used to identify and compare bacteria present within a given sample.

  3. Assess genomic relatedness between the donor and trial participants [ Time Frame: Up to 30 weeks; Days 1, 15, and 36 of each cycle ]
    Results of the stool or perirectal swab cultures obtained at the screening visit will be compared with the culture results from samples collected on Days 1, 15, and 36 of each cycle to characterize the genomic relatedness and microbiota changes between the donor and trial participants.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Ability to understand and willingness to sign a written informed consent document.
  • Ability and willingness to comply with study protocol requirements and receive the IND product via rectal retention enema, which was manufactured from a pre-selected stool donor participant.
  • History of MDRO infection with at least one of the following Target MDROs: CRE, VRE, ESBL, or MDR Pseudomonas.
  • Not on systemic antibiotics for any reason other than if MDRO infection was recent and potential participant is still taking antibiotics for target MDRO at time of screening. If the latter, then participant must complete antibiotic course by Study Day -2
  • Stool or Perirectal swab sampling with a positive Target MDRO (e.g CRE, VRE, ESBL, and/or MDR Pseudomonas) result within two weeks prior to enrollment, confirmed by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
  • Prior receipt of a living or deceased donor renal transplant.
  • Performance status of either: American Society of Anesthesiology (ASA) Classification Score of I-III, Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2, or Karnofsky Performance Score (KPS) of 50-100%.
  • At least one prior course of systemic antibiotics since renal transplant.
  • If applicable, willingness to discontinue probiotics or other microbiota restoration therapies during screening at least seven days prior to the first intervention.
  • The effects of FMT on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Negative blood or urine human chorionic gonadotropin (hCG) testing on the day of FMT for WOCBP with documentation of negative test result
  • Negative baseline Human Immunodeficiency Virus (HIV) test
  • Known screening drug monitoring level (e.g., tacrolimus); not subjected to screening window
  • Known serology CMV status confirmed either by Medical History (if positive). If no mention of positivity in medical records, serology is tested within 30 days of enrollment for:

    1. Cytomegalovirus (CMV) by polymerase chain reaction (PCR)
    2. Cytomegalovirus (CMV), serology Immunoglobulin G (IgG)

Exclusion Criteria:

  • Female participants who are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of IND product).
  • Prior gastrointestinal surgery or intervention:

    1. Ileostomy (in the last 3 months)
    2. Colostomy (in the last 3 months)
    3. Gastric or colon resection (in the last 3 months)
    4. Bariatric surgery (any prior history)
    5. Total colectomy (any prior history)
  • Any of the following gastrointestinal conditions:

    1. Irritable Bowel Syndrome (IBS) with diarrhea in the last 12 months
    2. Crohn's disease
    3. Ulcerative Colitis
    4. Celiac disease
    5. Untreated in-situ colorectal cancer
    6. Microscopic or ulcerative colitis
    7. Toxic megacolon or ileus
    8. Tube feeding (current or planned)
  • Known positive stool studies or cultures in the last 30 days for:

    1. Ova
    2. Parasites
    3. Salmonella
    4. Shigella
    5. Campylobacter
    6. Clostridium difficile (an enteropathogen) as tested by the Xpert C. difficile platform
    7. Other enteropathogens - defined as any positive result on the Biofire FilmArray Gastrointestinal Panel, (Campylobacter, Plesiomonas, Salmonella, Vibrio, Yersinia, Enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), Shigella, Cryptosporidium, Cyclospora, Entamoeba, Giardia, Adenovirus, Astrovirus, Norovirus, Rotavirus, Sapovirus).
  • Known uncontrolled intercurrent illness(es) such as, but not limited to:

    1. Ongoing or active infection
    2. Symptomatic congestive heart failure
    3. Unstable angina pectoris
    4. Cardiac arrhythmia
    5. Any other intercurrent acute illness that in the opinion of the investigator will preclude subject from entering the study
  • Compromised immune system other than transplant immunosuppression:

    1. HIV-positive as identified by one of the following:

      1. Positive HIV 1/2 antibody test result
      2. Positive HIV p24 antigen test result
      3. Prior diagnosis of HIV
      4. Active or history of administration of combination antiretroviral therapy (cART)
    2. Known Absolute Neutrophil (ANC) <1000 neutrophils per cubic millimeter (mm^3) in the last 3 months
    3. Active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment either concurrently or in the last 2 months
    4. Acute leukemia
    5. History of bone marrow transplantation (allogeneic or autologous) in the last 3 years
  • History of organ transplant rejection in the last 6 months
  • Significant food allergy to foods that are part of the stool donor participant's diet.
  • Life expectancy is 24 weeks or less.
  • Any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to:

    1. Known active intravenous drug or alcohol abuse
    2. Psychiatric illness
    3. Social situation
  • Participated in an investigational study that also meets one of the following criteria:

    1. Received an interventional agent (drug, device, or procedure) in the last 28 days
    2. Enrollment on this study or any other interventional study for MDROs

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 identifier (NCT number): NCT02922816

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Contact: Colleen S Kraft, MD, MSc

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United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30324
Contact: Colleen S. Kraft, MD    404-712-8889   
Principal Investigator: Colleen S. Kraft, MD, MSc         
Sponsors and Collaborators
Emory University
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Principal Investigator: Colleen S Kraft, MD, MSc Emory University
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Responsible Party: Colleen S Kraft, MD, MSc, Associate Professor, Emory University Identifier: NCT02922816    
Other Study ID Numbers: IRB00090101
First Posted: October 4, 2016    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified sequence data from 16S microbiome sequencing may be made available to an outside bioinformatics collaborator.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Colleen S Kraft, MD, MSc, Emory University:
Carbapenem-resistant Enterobacteriaceae (CRE)
Vancomycin-resistant Enterococcus (VRE)
Multidrug Resistant Organism (MDRO)
Fecal Microbiota Transplant (FMT)
Renal Transplant
Antibiotic Resistance
Multidrug Resistant (MDR) Pseudomonas
Additional relevant MeSH terms:
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Communicable Diseases