Fecal Microbiota Transplantation for Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease

Fecal Microbiota Transplantation for Treatment of Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease- a Pilot Study

The investigators hypothesize that perturbations in the intestinal microbiota following allogeneic hematopoietic stem cell transplantation (HSCT) are essential for the development and propagation of acute graft-versus-host disease. Therefore, modification of HSCT recipients' gut microbiota using fecal transplantation from a healthy donor could be used to treat gut acute GVHD.

The study evaluates safety and feasibility of fecal microbiota transplantation with frozen capsules from healthy donors for the treatment of steroid resistant or steroid dependent acute graft-versus-host disease of the gut.

Study Overview

• Status: Unknown
• Conditions: Stem Cell Transplant Complications; Fecal Microbiota Transplantation; Graft Versus Host Disease, Acute
• Intervention / Treatment: Biological: Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Recruiting
    • Chaim Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults (ages 18 to 75 years) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and developed gut acute Graft-versus-Host Disease (aGvHD).
• Participants have steroid-resistant or steroid-dependent gut aGvHD.
• Steroid resistant gut aGvHD is defined as cases in which gastrointestinal symptoms do not improve within 7 days after initial steroid therapy (≥1 mg/kg of methylprednisolone) or clear progression after 5 days.)
• Steroid-dependent gut aGVHD is defined as cases in which reduction of steroid dose was not possible due to exacerbation of gastrointestinal symptoms.
• Participants may have undergone allogeneic HSCT for any diagnosis at any time prior to developing aGvHD, and are not restricted to any specific conditioning regimen or by the subsequent administration of donor lymphocyte infusion.
• Participants should be able to give informed consent.

Exclusion Criteria:

• Participants may not have gut aGvHD which permits the tapering of steroid dose.
• Participants may not have ongoing, uncontrolled infection (i.e. unresolved bacteremia, uncontrolled CMV infection).
• Participants may not have ongoing enteritis primarily caused by enteropathy other than gut GvHD, excluding resistant clostridium difficile infection.
• Participants may not have acute neutrophil count < 500 cells/µL.
• Participants may not have toxic megacolon
• Participants may not have active gastrointestinal bleeding.
• Participants may not be pregnant or lactating.
• Participants may not be unable to swallow pills.

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: Fecal Microbiota Transplantation (FMT); Participants will receive a single dose of oral FMT, which is 15 capsules per day for 2 consecutive days (total of 30 capsules). All capsules administered to a participant are from the same unrelated donor. Participants will be asked to fast for 4 hours prior to and 1 hour following capsule intake. Participants will be asked to drink at least 360cc of water during administration. Treatment will be administered on an inpatient basis. In patients with no/partial response, the FMT may be repeated from the same or a different donor. Subjects receiving any amount of the FMT capsules will be followed for at least 6 months.Stool and blood samples will be serially collected.

Biological: Fecal Microbiota Transplantation; Thirty fecal microbiota capsules produced from a single healthy donor, unrelated to the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events	Participants will be evaluated for serious adverse events (SAEs) relating to FMT occurring within 28 days following transplantation. SAEs are defined as any adverse experience occurring during or after FMT that results in any of the following outcomes: death, life-threatening experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity or an important medical event events	28 days following FMT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-serious adverse events	Participants will be evaluated for non-serious adverse events relating to FMT within 28 days following transplantation. Non-serious adverse events are defined as diarrhea, nausea and vomiting, fatigue and malaise, headache, and distension/bloating/abdominal discomfort/pain	28 days following FMT.
Gut acute Graft-versus-Host Disease (aGvHD) response.	Participants will be evaluated on days 7 and 28 following transplantation for response to therapy. Response criteria for steroid-resistant patients is as follows: Complete response: resolution of all gastrointestinal signs and symptoms; Partial response: decrease in severity of gut GVHD by at least one stage; Progression: Progressive worsening of gut GVHD; No change: No significant change in gut GVHD Response criteria for steroid-dependent patients is as follows: Complete response: reduction of the steroid dose to 5 mg or less of prednisone (or a steroid equivalent) per day.; Partial response: a reduction of ≥40% in the dose of steroid; Progression: an increase of >=10% in the steroid dose; No change: any other option	up to 28 days following FMT.
aGvHD severity	Participants will be evaluated on days 7 and 28 following transplantation for severity of aGvHD. aGVHD severity is graded by the International Bone Marrow Transplant Registry Severity Index grading system	up to 28 days following FMT.
Reduction in the dose of steroids.	The dose of methylprednisolone, or an equivalent GCS, will be evaluated on day 7, and 28. The change in the dose at day 28, adjusted to the type of GCS used.	up to 28 days following FMT.

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Roni Shouval, MD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2017
• Primary Completion (Anticipated): July 20, 2019
• Study Completion (Anticipated): December 20, 2019

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: April 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Hematopoietic Stem Cell Transplantation; Intestinal Acute Graft Versus Host Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Disease Attributes; Acute Disease; Graft vs Host Disease
• Other Study ID Numbers: 3822-16-SMC (Other Identifier: Sheba Medical Center, Tel-HaShomer, Israel)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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