Dysbiosis and Immune Reconstitution After Allo-HSCT (PARI-DYS)

Intestinal Dysbiosis and Immune Reconstitution After Allogeneic Hematopoietic Cell Transplantation

Preliminary (proof of concept), monocentric, interventional, prospective, non-randomized and analytic trial designed to simultaneously explore intestinal microbiota changes and early post-transplant immune reconstitution, and to correlate biological data with clinical data (antibiotics use, stress level, GVHD).

Study Overview

• Status: Unknown
• Conditions: Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Biological: blood samples; Biological: fecal samples; Behavioral: Anxiety test; Behavioral: Stress test

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major curative therapeutic approach for hematologic neoplasms. After HSCT, patients have a compromised GI mucosal barrier and an altered microbiota, also called dysbiosis. The later could be due to conditioning or use of broad-spectrum antibiotics, and could be accentuate by stress encountered by patients during their therapy management. Recent data have shown that alterations in the intestinal flora are associated with bad outcome, particularly with graft-versus-host disease (GVHD), bacteremia, and reduced overall survival post-transplantation. How intestinal bacteria can modulate the risk of relapse after HSCT is yet unknown. The scientists hypothesize that the variation of some bacterial taxa may influence post-transplant immune reconstitution, particularly invariant Natural Killer T cells.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Corentine ALAUZET, Dr; Phone Number: +33 0383153938; Email: c.alauzet@chru-nancy.fr
• Study Contact Backup: Name: Marie-Thérèse RUBIO, Pr; Phone Number: +33 0383153257; Email: m.rubio@chru-nancy.fr

Study Locations

• France
  • Vandoeuvre Les Nancy, France, 54511
    • Recruiting
    • RUBIO Marie-Thérèse
    • Contact: Marie-Thérèse RUBIO, PU-PH; Phone Number: 383153282

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients > 18 years affiliated to a social security system
• Patients followed at the hospital of Nancy for a allogeneic hematopoietic cell transplantation (HLA matched donor)
• Graft of peripheral blood stem cell
• GVHD prophylaxis by ciclosporin and antilymphocyte serum +/- mycophenolate mofetil or methotrexate.

Exclusion Criteria:

• HIV+ patients
• Patients with active HBV or HCV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient; For all patients included in the study, the following interventions will be performed : several blood samples (quantity collected requiring classification of this study as interventional according to French law); several fecal samples; anxiety tests; stress tests	Biological: blood samples; 20 to 30 ml of blood sample (D0, D15, D30, D60, D90, D180, Y1, Y2); Biological: fecal samples; 1 g of feces (D-8, D0, D15, D30, D90); Behavioral: Anxiety test; Test of Spielberger; Behavioral: Stress test; Test of Cohen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
quality of iNKT reconstitution after HSCT (good/poor)	Day 90,

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gut microbiota composition	relative abundance of intestinal bacterial taxa	Day 0, Day 15, Day 30, Day 90
immune reconstitution after HSCT (other immune cells)	quantification of Tregs, MDSC, MAIT, T lymphocytes	Day 15, Day 30, Day 60, Day 90, Day 180, Year 1, Year 2
GVH disease	yes/not	Day 30, Day 60, Day 90
use of antibiotics	yes/not (molecules, delay, posology)	Day 0, Day 15, Day 30, Day 60, Day 90
level of stress	test of Cohen	Day -8, Day 15, Day 30, Day 90
level of anxiety	test of Spielberger	Day -8, Day 15, Day 30, Day 90
quality of iNKT reconstitution after HSCT (good/poor)		Day 15, Day 30, Day 60, Day 180, Year 1, Year2

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Anticipated): January 31, 2021
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: immune reconstitution; HSCT; intestinal dysbiosis
• Additional Relevant MeSH Terms: Pathologic Processes; Dysbiosis
• Other Study ID Numbers: 2018-A00676-49

Drug and device information, study documents

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