Ignite Creation Date:
2024-05-06 @ 7:33 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06058572
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-10-16
First Post:
2023-09-21
Brief Title:
Effect of Rifaximin on Gut Bacterial Flora Post Stem Cell Transplant in Patients With Acute Leukemia
Sponsor:
Tata Memorial Centre
Organization:
Tata Memorial Centre
Study Overview
Official Title:
Randomized Trial to Study the Effect of Rifaximin on Gut Microbiome Diversity Post Allogeneic Stem Cell Transplant in Acute Leukemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Goal This study is a randomized phase II interventional study The purpose of this study is to see if addition of oral rifaximin tablets during allogeneic stem cell transplant can improve the quality of gut microbiome and reduce chances of death infections and graft versus host disease GVHD post-transplant
The study objectives are as follows
Primary Objective To determine the impact of rifaximin on gut microbial diversity and compare it with controls
Secondary Objectives a To determine non-relapse mortality at 1-year post transplant in patients who receive peri-transplant transplant rifaximin and compare it with controls
b To compare the incidence of severe GVHD in patients who receive peri-transplant rifaximin with the controls
c To determine impact of gut decontamination with rifaximin on incidence of MDR sepsis and usage of higher antibiotics eg Carbapenems colistin tigecycline ceftazidime avibactum and ceftriaxone-sulbactam EDTA in first 6 months post BMT
d To determine the impact of rifaximin induced gut manipulation on immune reconstitution T cell repertoire post-transplant and cytokine profile
Exploratory objective To use single cell transcriptomics SCT to identify immune cell profile in gut biopsies post allogeneic stem cell transplant whenever biopsy is done to correlate the impact of microbiome on gut immunity
Intervention Tab Rifaximin 200 mg will be given orally twice daily from day -8 to day 60 of allogeneic stem cell transplant in acute leukemia patients This will be in addition to standard of care post-transplant treatment
Comparator Agent Standard of care treatment including standard anti GVHD measures antibiotic support and transfusions as needed
The study objectives are as follows
Primary Objective To determine the impact of rifaximin on gut microbial diversity and compare it with controls
Secondary Objectives a To determine non-relapse mortality at 1-year post transplant in patients who receive peri-transplant transplant rifaximin and compare it with controls
b To compare the incidence of severe GVHD in patients who receive peri-transplant rifaximin with the controls
c To determine impact of gut decontamination with rifaximin on incidence of MDR sepsis and usage of higher antibiotics eg Carbapenems colistin tigecycline ceftazidime avibactum and ceftriaxone-sulbactam EDTA in first 6 months post BMT
d To determine the impact of rifaximin induced gut manipulation on immune reconstitution T cell repertoire post-transplant and cytokine profile
Exploratory objective To use single cell transcriptomics SCT to identify immune cell profile in gut biopsies post allogeneic stem cell transplant whenever biopsy is done to correlate the impact of microbiome on gut immunity
Intervention Tab Rifaximin 200 mg will be given orally twice daily from day -8 to day 60 of allogeneic stem cell transplant in acute leukemia patients This will be in addition to standard of care post-transplant treatment
Comparator Agent Standard of care treatment including standard anti GVHD measures antibiotic support and transfusions as needed
Detailed Description:
The gut microbiome plays a significant role in modulating the immune re-constitution post allogeneic stem cell transplant ASCT Low gut microbial diversity has been consistently associated with poor outcomes of transplant including increased incidence of acute graft versus host disease aGVHD post-transplant bacterial sepsis and non-relapse mortality NRM However the exact mechanism by which gut microbiome influences local as well as systemic immunity is not completely known and is thought to be due to the impact of microbial metabolites on intestinal epithelial cells and host antigen-presenting cells Understanding these mechanisms and modulating the microbiome may be crucial to improving transplant outcomes Rifaximin is a locally acting antibiotic that has been approved for manipulating the gut microbiome in hepatic failure It is unique because of its ability to clear pathogenic bacteria while preserving the anaerobic commensals It can potentially modify the gut microbiome to increase the alpha diversity and this may help reduce aGVHD infectious complications and mortality post-transplant High incidence of multidrug resistant sepsis and frequent use of broad spectrum antibiotics in India would result in higher rates of dysbiotic gut- making microbiome manipulation to improve transplant outcomes more relevant in our country We are proposing a randomized controlled trial to understand the benefits of modulating the gut microbiome in patients of ASCT while investigating the local and global immune repertoire using single cell sequencing and multicolour flow cytometry
Study design Single center open-labeled phase II study randomized controlled trial
Primary Objective To determine the impact of rifaximin on gut microbial alpha diversity and compare it with controls
Secondary Objectives
To determine impact of rifaximin on 1 year non relapse mortality post-transplant incidence of grade IIIIV aGVHD incidence of MDR sepsis patterns of immune cell reconstitution and cytokine profile post-transplant
Exploratory objective To use single-cell transcriptomics SCT to identify immune cell profiles in gut biopsies post ASCT in order to get insights into the impact of the microbiome on local gut immunity
Study population Adult patients who undergo ASCT at the Tata Memorial Centre
Study Methodology in brief Patients would be randomized to receive either oral tablet rifaximin 200 mg twice daily along with standard posttransplant treatment or to receive standard of care treatment alone Stool samples and blood samples will be collected at different time points for microbiome analysis and immune cell profiling respectively We plan to perform 16s rRNA-based next-generation sequencing of all variable regions using a phased primer approach using stool DNA as a template Gut microbiome diversity will be calculated using the inverse Simpson index Immune cell profile would be analyzed using 16 color flow cytometry In selected cases where patients undergo colonoscopic gut biopsy for aGVHD we will also obtain samples for transcriptome sequencing This will help us understand how immune cells interact with gut mucosa and microbiome in patients of aGVHD
Study design Single center open-labeled phase II study randomized controlled trial
Primary Objective To determine the impact of rifaximin on gut microbial alpha diversity and compare it with controls
Secondary Objectives
To determine impact of rifaximin on 1 year non relapse mortality post-transplant incidence of grade IIIIV aGVHD incidence of MDR sepsis patterns of immune cell reconstitution and cytokine profile post-transplant
Exploratory objective To use single-cell transcriptomics SCT to identify immune cell profiles in gut biopsies post ASCT in order to get insights into the impact of the microbiome on local gut immunity
Study population Adult patients who undergo ASCT at the Tata Memorial Centre
Study Methodology in brief Patients would be randomized to receive either oral tablet rifaximin 200 mg twice daily along with standard posttransplant treatment or to receive standard of care treatment alone Stool samples and blood samples will be collected at different time points for microbiome analysis and immune cell profiling respectively We plan to perform 16s rRNA-based next-generation sequencing of all variable regions using a phased primer approach using stool DNA as a template Gut microbiome diversity will be calculated using the inverse Simpson index Immune cell profile would be analyzed using 16 color flow cytometry In selected cases where patients undergo colonoscopic gut biopsy for aGVHD we will also obtain samples for transcriptome sequencing This will help us understand how immune cells interact with gut mucosa and microbiome in patients of aGVHD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None