Autologous Fecal Microbiota Transplantation for Patients With Acute Graft-versus-Host Disease

This study aims to assess the safety and efficacy of autologous fecal microbiota transplantation (FMT) in gastrointestinal (GI) related graft-versus-host disease (GVHD). Stool for FMT will be prepared from pre-allogeneic stem cell transplantation (Allo-SCT) period. This strategy might offer a novel and safe therapeutic approach for these patients, who suffer from high disease related morbidity and mortality and are refractory to multiple treatments.

Study Overview

• Status: Withdrawn
• Conditions: Fecal Microbiota Transplantation in Graft vs. Host Disease
• Intervention / Treatment: Biological: Autologous Fecal Microbiota Transplantation

Detailed Description

All candidates for Allo-SCT at BMT unit in RHCC will be screened for study inclusion and exclusion criteria. Seven to fourteen days prior to Allo-SCT (before initiation of SCT related antimicrobials), all consenting patients will supply stool sample (first stool sample), which will serve as the autologous FMT sample, and clinical data will be collected. Patients who will develop GI related GVHD will be asked to supply another stool sample 7±2 days after the appearance of GVHD related symptoms (second stool sample). Clinical and laboratory data will be collected. Another stool sample will be collected 7-14 following autologous FMT (third stool sample), and clinical data and outcome will be documented. Day 1 of the study will be defined as day of Allo-SCT, and follow up period is 6 months. Complementary data will be collected from the electronic medical records.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Health Care Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

* Allo-SCT patients above 18 years of age with acute steroid-resistant GI-related GVHD grade III-IV.

Exclusion Criteria:

• Prior inclusion to an interventional study
• Pregnant or lactating women
• Previous Allo-SCT
• Known multi-drug resistance carriage prior to stool collection
• Severe colitis of any etiology or a history of inflammatory bowel disease (IBD)
• Uncontrolled infection (hemodynamic instability, ongoing fever or bacteremia within 3 days after antibiotics administration)
• Active GI bleeding
• Absolute neutrophil count < 500 cells/microL
• Patients who cannot give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Allo-SCT patients with GI related GVHD; Allo-SCT patients above 18 years of age with acute steroid-resistant GI-related GVHD grade III-IV. The diagnosis of GVHD will be made on clinical grounds (in line with the major associations' recommendations) - the appearance of characteristic mucoid diarrhea within 100 days after Allo-SCT, with or without associated skin/liver involvement. In cases of atypical presentation - we will recommend biopsy or endoscopy for diagnosis. Patients suspected to have Clostridium difficille associated diarrhea will be tested for toxin (CDT). Steroid-resistant GI-related GVHD will be defined as lack of improvement (same stage) or worsening of GI symptoms after 7 days of steroid therapy (≥ 2 ml/kg of IV methylprednisolone).

Biological: Autologous Fecal Microbiota Transplantation; Consenting allo- SCT patients with acute steroid-resistant GI-related GVHD grade III-IV will receive autologous FMT by nasogastric tube. Standardized stool suspension will be given once a day for two consecutive days.In order to prevent aspiration, patients will be kept in a 45ᵒ upright position for four hours. Participants will fast the night before and be treated with proton pump inhibitors prior to each FMT. In cases where complete response was not obtained within 7 days after autologous FMT, patients may be eligible for another trail of autologous FMT or to switch to other pharmacological interventions. Stool samples will be collected before and after the intervention for microbial analyses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of severe adverse events (SAEs) related to autologous FMT	Development of SAEs related to autologous FMT within 7 days after the intervention. SAEs include mortality, bacteremia, and radiological-proven aspiration pneumonia requiring mechanical ventilation.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		90 days
Complete or partial response of GI-related GVHD after each FMT	Patients will be evaluated 90 days following FMT for symptoms severity and response. Response is defined as: Complete response - resolution of all GI symptoms; Partial response - decrease of severity of GI-related GVHD by at least one stage or ability to taper steroids to <0.5 mg/kg; No response - progression of symptoms or no change in GI symptoms	90 days
Non-severe adverse events (AE)	Non-severe adverse events including dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, fever, or aspiration not requiring mechanical ventilation. Each AE will be graded.	7 days
Change in microbiota composition after each FMT		180 days

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): March 5, 2020
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: April 7, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: microbiome; allogeneic stem cell transplantation; Fecal microbiota transplantation
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: rambam207

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No