Microbiome Alterations in IL10RA-deficient Patients After HSCT

Longitudinal Development of Intestinal Microbiome in IL10RA-deficient Patients After Hematopoietic Stem Cell Transplantation

To elucidate the longitudinal development of intestinal microbiota in patients with IL10RA deficiency after hematopoietic stem cell transplantation (HSCT). The investigators planned to collect fecal samples from IL10RA-deficient patients who received HSCT. Samples were collected more than once every three days after engraftment in lamina flow ward and at least once a week before discharge. Microbial DNA was extracted from the fecal samples. And all analysis was based on the next generation sequencing data.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Diseases; Microbiota
• Intervention / Treatment: Procedure: hematopoietic stem cell transplantation

Detailed Description

Hematopoietic stem cell transplantation is considered the only curative therapy for patients with interleukin-10 receptor-A(IL10RA) deficiency. The investigators aimed to collect the fecal samples of these patients throughout the conditioning, transplantation until discharge, providing a dense insight into the longitudinal development of intestinal microbiota.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 6 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who were diagnosed with IL10RA deficiency and who received the hematopoietic stem cell transplantation in a tertiary hospital were enrolled.

Description

Inclusion Criteria:

• IL10RA gene mutations;
• Eligible for hematopoietic stem cell transplantation.

Exclusion Criteria:

• Unwilling to participate.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

HSCT cohort; IL10RA-deficient patients who received hematopoietic stem cell transplantation

Procedure: hematopoietic stem cell transplantation; Reduced intensity conditioning(RIC) chemotherapy regimen before transplantation; All patients were cared for in single rooms ventilated with a highly effective particulate air filtration system. All patients received intravenous immunoglobulin and antimicrobial prophylaxis, which included antiviral, antifungal, and Pneumocystis jirovecii prophylaxis with ganciclovir and micafungin, as per routine clinical practice before transplantation.; Umbilical cord blood transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shannon indices	Shannon index is a popular diversity index in the ecological literature; minimum score is zero, higher values represent a better outcome	during the hospitalization of each eligible patient, an average of 90 days per patient
Simpson indices	Simpson index in ecology is to measure the degree of concentration when individuals are classified into types; scale ranges [0,1]; lower values represent a better outcome	during the hospitalization of each eligible patient, an average of 90 days per patient
relative abundance of Proteobacteria	describe the microbiome at the phylum level	during the hospitalization of each eligible patient, an average of 90 days per patient
relative abundance of Firmicutes	describe the microbiome at the phylum level	during the hospitalization of each eligible patient, an average of 90 days per patient
Clostridium sensus_stricto_1	describe the microbiome at the genus level	during the hospitalization of each eligible patient, an average of 90 days per patient
Escherichia - Shigella	describe the microbiome at the genus level	during the hospitalization of each eligible patient, an average of 90 days per patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
chimerism	The level of chimerism of each patient will be reported as percentages [0,100%]	during the hospitalization of each eligible patient, an average of 90 days per patient
manifestation of graft-versus-host disease	describe the graft-versus-host disease happened to each patient	during the hospitalization of each eligible patient, an average of 90 days per patient
Sobs indices	describe the the observed richness of each sample	during the hospitalization of each eligible patient, an average of 90 days per patient
Chao1 estimator	describe the operational taxonomic unit(OTU) numbers of each sample	during the hospitalization of each eligible patient, an average of 90 days per patient
neutrophil cell count	blood test results	during the hospitalization of each eligible patient, an average of 90 days per patient
platelet count	blood test results	during the hospitalization of each eligible patient, an average of 90 days per patient

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
relative abundance of Clostridiales	describe the microbiome at the order level	during the hospitalization of each eligible patient, an average of 90 days per patient
Shannoneven indices	measure the community evenness, scale ranges [0,1]; higher values represent a better outcome	during the hospitalization of each eligible patient, an average of 90 days per patient
Simpsoneven indices	measure community evenness, scale ranges [0,1]; higher values represent a better outcome	during the hospitalization of each eligible patient, an average of 90 days per patient

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Principal Investigator: Ying Huang, MD, Children's Hospital of Fudan University

Publications and helpful links

General Publications

• Peng K, Qian X, Huang Z, Lu J, Wang Y, Zhou Y, Wang H, Wu B, Wang Y, Chen L, Zhai X, Huang Y. Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency. Inflamm Bowel Dis. 2018 Jun 8;24(7):1416-1427. doi: 10.1093/ibd/izy028.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: interleukin 10 receptor alpha gene
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases
• Other Study ID Numbers: HSCT microbiomte

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No