Back to resultsFecal Microbiota Transplantation for Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease
Primary Purpose
Stem Cell Transplant Complications, Graft Versus Host Disease, Acute, Fecal Microbiota Transplantation
Status
Unknown status
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Stem Cell Transplant Complications focused on measuring Fecal Microbiota Transplantation, Intestinal Acute Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation
Eligibility 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.
Sites / Locations
- Chaim Sheba Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fecal Microbiota Transplantation (FMT)
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03214289
Brief Title
Fecal Microbiota Transplantation for Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease
Official Title
Fecal Microbiota Transplantation for Treatment of Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease- a Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Unknown status
Study Start Date
July 12, 2017 (Actual)
Primary Completion Date
July 20, 2019 (Anticipated)
Study Completion Date
December 20, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sheba Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stem Cell Transplant Complications, Graft Versus Host Disease, Acute, Fecal Microbiota Transplantation
Keywords
Fecal Microbiota Transplantation, Intestinal Acute Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fecal Microbiota Transplantation (FMT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Fecal Microbiota Transplantation
Intervention Description
Thirty fecal microbiota capsules produced from a single healthy donor, unrelated to the participant.
Primary Outcome Measure Information:
Title
Serious adverse events
Description
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
Time Frame
28 days following FMT.
Secondary Outcome Measure Information:
Title
Non-serious adverse events
Description
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
Time Frame
28 days following FMT.
Title
Gut acute Graft-versus-Host Disease (aGvHD) response.
Description
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
Time Frame
up to 28 days following FMT.
Title
aGvHD severity
Description
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
Time Frame
up to 28 days following FMT.
Title
Reduction in the dose of steroids.
Description
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.
Time Frame
up to 28 days following FMT.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roni Shouval, MD
Phone
972-3-5305830
Email
roni.shoval@sheba.health.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roni Shouval, MD
Organizational Affiliation
Sheba Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
Country
Israel
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Fecal Microbiota Transplantation for Steroid Resistant and Steroid Dependent Gut Acute Graft Versus Host Disease
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