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

• ClinicalTrials.gov Identifier: NCT03214289
• Recruitment Status: Unknown
• First Posted: July 11, 2017
• Last Update Posted: April 9, 2018
• Sponsor: Sheba Medical Center
• Information provided by (Responsible Party): Dr. Shouval Roni, Sheba Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Stem Cell Transplant Complications; Graft Versus Host Disease, Acute; Fecal Microbiota Transplantation	Biological: Fecal Microbiota Transplantation	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fecal Microbiota Transplantation for Treatment of Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease- a Pilot Study
• Actual Study Start Date: July 12, 2017
• Estimated Primary Completion Date: July 20, 2019
• Estimated Study Completion Date: December 20, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Serious adverse events [ Time Frame: 28 days following FMT. ]
   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

Secondary Outcome Measures :

1. Non-serious adverse events [ Time Frame: 28 days following FMT. ]
   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
2. Gut acute Graft-versus-Host Disease (aGvHD) response. [ Time Frame: up to 28 days following FMT. ]

   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
3. aGvHD severity [ Time Frame: up to 28 days following FMT. ]

   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

4. Reduction in the dose of steroids. [ Time Frame: up to 28 days following FMT. ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Roni Shouval, MD; 972-3-5305830; roni.shoval@sheba.health.gov.il

Locations

Israel

Chaim Sheba Medical Center; Recruiting

Ramat Gan, Israel

Sponsors and Collaborators

Sheba Medical Center

Investigators

• Principal Investigator: Roni Shouval, MD; Sheba Medical Center

More Information

• Responsible Party: Dr. Shouval Roni, Principal Investigator, Hematology and BMT Division, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT03214289
• Other Study ID Numbers: 3822-16-SMC; 3822-16-SMC ( Other Identifier: Sheba Medical Center, Tel-HaShomer, Israel )
• First Posted: July 11, 2017
• Last Update Posted: April 9, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. Shouval Roni, Sheba Medical Center:

Fecal Microbiota Transplantation; Intestinal Acute Graft Versus Host Disease; Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:

Graft vs Host Disease; Acute Disease; Immune System Diseases; Disease Attributes; Pathologic Processes