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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03492502
Recruitment Status : Not yet recruiting
First Posted : April 10, 2018
Last Update Posted : August 31, 2018
Information provided by (Responsible Party):
Haggai Bar-Yoseph MD, Rambam Health Care Campus

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fecal Microbiota Transplantation in Graft vs. Host Disease Biological: Autologous Fecal Microbiota Transplantation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Fecal Microbiota Transplantation for Patients With Acute Graft-versus-Host Disease
Estimated Study Start Date : November 1, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : April 30, 2019

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.

Primary Outcome Measures :
  1. Development of severe adverse events (SAEs) related to autologous FMT [ Time Frame: 7 days ]
    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.

Secondary Outcome Measures :
  1. Complete or partial response of GI-related GVHD after each FMT [ Time Frame: 90 days ]

    Patients will be evaluated 90 days following FMT for symptoms severity and response. Response is defined as:

    1. Complete response - resolution of all GI symptoms
    2. Partial response - decrease of severity of GI-related GVHD by at least one stage or ability to taper steroids to <0.5 mg/kg
    3. No response - progression of symptoms or no change in GI symptoms

  2. Non-severe adverse events (AE) [ Time Frame: 7 days ]
    Non-severe adverse events including dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, fever, or aspiration not requiring mechanical ventilation. Each AE will be graded.

  3. Mortality [ Time Frame: 90 days ]
  4. Change in microbiota composition after each FMT [ Time Frame: 180 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03492502

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Rambam Health Care Campus Not yet recruiting
Haifa, Israel
Contact: Haggai Bar-Yoseph, MD         
Sponsors and Collaborators
Rambam Health Care Campus

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Responsible Party: Haggai Bar-Yoseph MD, Principal investigator, Rambam Health Care Campus Identifier: NCT03492502     History of Changes
Other Study ID Numbers: rambam207
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Haggai Bar-Yoseph MD, Rambam Health Care Campus:
Fecal microbiota transplantation
allogeneic stem cell transplantation
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases