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

Stem Cell Transplant Complications Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03214289
• Other study ID #: 3822-16-SMC
• Secondary ID: 3822-16-SMC
• Status: Recruiting
• Phase: Phase 1
• First received: June 29, 2017
• Last updated: April 5, 2018
• Start date: July 12, 2017
• Est. completion date: December 20, 2019

Study information

• Verified date: April 2018
• Source: Sheba Medical Center
• Contact: Roni Shouval, MD
• Phone: 972-3-5305830
• Email: roni.shoval[@]sheba.health.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4
• Est. completion date: December 20, 2019
• Est. primary completion date: July 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Disease
• Fecal Microbiota Transplantation
• Graft Versus Host Disease, Acute
• Graft vs Host Disease
• Stem Cell Transplant Complications

Intervention

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

Locations

Country	Name	City	State
Israel	Chaim Sheba Medical Center	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.