FMT for MDRO Colonization After Infection in Renal Transplant Recipients

NCT02922816 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IRB00090101
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Infection Due to Resistant Organism

Keywords

Carbapenem-resistant Enterobacteriaceae (CRE); Vancomycin-resistant Enterococcus (VRE); Multidrug Resistant Organism (MDRO); Fecal Microbiota Transplant (FMT); Renal Transplant; Colonization; Infection; Antibiotic Resistance; Resistome; Multidrug Resistant (MDR) Pseudomonas

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events

  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.

  Up to 30 weeks

• Change in Target MDRO Growth

  The primary outcome is target MDRO growth on perirectal swab or stool culture on Day 36 of each cycle compared Screening and Day 1 culture results. Participants will be classified as having a complete response, partial response, refractory response or progression based on their Day 36 culture results. Partial response, refractory response, and progression may be collapsed in a non-response category for analytic purposes.

  Day 1, Up to 30 weeks

Study Arms (2)

Control arm

PLACEBO COMPARATOR

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; Procedure: Stool or perirectal swab sampling

Fecal Microbiota Transplant (FMT)

EXPERIMENTAL

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); Procedure: Bowel preparation; Procedure: Stool or perirectal swab sampling; Other: Fasting

Interventions

Fecal Microbiota Transplant (FMT) BIOLOGICAL

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.

Fecal Microbiota Transplant (FMT)

Bowel preparation PROCEDURE

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

Control arm; Fecal Microbiota Transplant (FMT)

Stool or perirectal swab sampling PROCEDURE

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

Control arm; Fecal Microbiota Transplant (FMT)

Fasting OTHER

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.

Fecal Microbiota Transplant (FMT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to sign a written informed consent document.
• Ability and willingness to comply with study protocol requirements and receive an enema.
• History of MDRO infection with at least one of the following target MDROs: CRE, VRE, ESBL, or MDR Pseudomonas.
• Prior receipt of a renal transplant.
• If applicable, willingness to discontinue probiotics or other microbiota restoration therapies during screening at least seven days prior to study Day 1.
• 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 serology CMV status confirmed by Medical History (if positive). If no mention of positivity in medical records, serology is tested within 30 days of enrollment for:
• Cytomegalovirus (CMV) by polymerase chain reaction (PCR)
• Cytomegalovirus (CMV), serology Immunoglobulin G (IgG)

You may not qualify if:

• Female participants who are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of investigational product).
• Prior gastrointestinal surgery or intervention:
• Ileostomy (in the last 3 months)
• Colostomy (in the last 3 months)
• Gastric or colon resection (in the last 3 months)
• Bariatric surgery (any prior history)
• Total colectomy (any prior history)
• Any of the following gastrointestinal conditions:
• Irritable Bowel Syndrome (IBS) with diarrhea in the last 12 months
• Crohn's disease
• Ulcerative Colitis
• Celiac disease
• Untreated in-situ colorectal cancer
• Microscopic colitis
• Toxic megacolon or ileus

Sponsors & Collaborators

• Emory University: lead
• Cepheid: collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30324, United States

Location

Related Publications (2)

• Woodworth MH, Conrad RE, Haldopoulos M, Pouch SM, Babiker A, Mehta AK, Sitchenko KL, Wang CH, Strudwick A, Ingersoll JM, Philippe C, Lohsen S, Kocaman K, Lindner BG, Hatt JK, Jones RM, Miller C, Neish AS, Friedman-Moraco R, Karadkhele G, Liu KH, Jones DP, Mehta CC, Ziegler TR, Weiss DS, Larsen CP, Konstantinidis KT, Kraft CS. Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement. Sci Transl Med. 2023 Nov;15(720):eabo2750. doi: 10.1126/scitranslmed.abo2750. Epub 2023 Nov 1.

  PMID: 37910603 RESULT

• Woodworth MH, Kwon JH, Kraft CS. An Ounce of Prevention Is Equivalent to How Much Decolonization Exactly? Clin Infect Dis. 2021 Jun 1;72(11):e924. doi: 10.1093/cid/ciaa1524. No abstract available.

  PMID: 33029623 DERIVED

MeSH Terms

Conditions

Infections; Pseudomonas Infections

Interventions

Fecal Microbiota Transplantation; Cathartics; Defecation; Angptl4 protein, mouse

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Gastrointestinal Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Officials

• Colleen S Kraft, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 27, 2016
• First Posted: October 4, 2016
• Study Start: December 1, 2016
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Researchers interested in using data collected in this study should submit a methodologically sound protocol to the study PI.

Locations

US (1)