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.
- Study Type: Interventional
- Study Design
- Intervention Model: Single Group Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: April 30, 2019
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.
- 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.
Arms, Groups and Cohorts
- 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).
Clinical Trial Outcome Measures
- 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.
- 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: Complete response – resolution of all GI symptoms Partial response – decrease of severity of GI-related GVHD by at least one stage or ability to taper steroids to <0.5 mg/kg No response – progression of symptoms or no change in GI symptoms
- 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.
- Time Frame: 90 days
- Change in microbiota composition after each FMT
- Time Frame: 180 days
Participating in This Clinical Trial
* Allo-SCT patients above 18 years of age with acute steroid-resistant GI-related GVHD grade III-IV.
- 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
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Rambam Health Care Campus
- Provider of Information About this Clinical Study
- Principal Investigator: Haggai Bar-Yoseph MD, Principal investigator – Rambam Health Care Campus
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