AlloBolome: Metabolome and Microbiome Impact on Acute GVHD in Recipients of Hematopoietic Transplant

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05186857

Collaborator

Instituto de Salud Carlos III (Other)

120

Enrollment

Locations

42.5

Anticipated Duration (Months)

13.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recent published data suggest that specific alterations in intestinal metabolome signature of hematopoietic stem cell transplant (allo-SCT) recipients might influence incidence and severity of acute graft versus host disease (aGVHD). Nevertheless, this possible relationship has not been undoubtedly established, pathophysiologic mechanisms have not been elucidated and possible clinical implications have not been studied. We hypothesized that in the early phase of allo-SCT, specific alterations in faecal metabolome occurred related to loss of intestinal microbiota diversity and disbalance of specific bacterial taxa, and that both alterations determine reduced survival of patients through increased incidence and severity of aGVHD. To test this hypothesis, a prospective multi-center cohort of allo-SCT recipients will had faecal and plasmatic samples collected at predetermined time-points pre&post-allo-SCT, and clinical relevant variables will be prospectively recorded throughout two years posttransplant follow-up. Metabolomic and microbiome analysis will be done to answer objectives of the study. To additionally explore if differential evolving characteristics in the intestinal metabolome and microbiome of donor/recipient sibling pairs influence the incidence and severity of aGVHD, probability of malignancy relapse and early and late mortality an additional cohort of family donors of enrolled patients will also have faecal and plasmatic samples collected and analysed.

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Impact of Intestinal Metabolome and Microbiome Disbalance of Recipients of Hematopoietic Transplant in the Development of Acute Graft Versus Host Disease.

Anticipated Study Start Date :

Sep 15, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2026

Outcome Measures

Primary Outcome Measures

Metabolome [From pre-Conditioning (Day -15) to Day +100 post-transplant.]
Sequential pre-transplant/post-transplant modifications in faecal and plasmatic levels of: 1.a. Butyrate (targeted analysis), 1.b: Biliary acids (targeted analysis) and 1.c. Metabolomic signature (untargeted analysis).
Incidence of Acute graft versus host disease [From the day of transplant (Day 0) to Day +100 posttransplant.]
Comparison of the incidence of any degree, degree-II and degree-III/IV of acute graft versus host disease between sub-groups of patients defined according to obtained metabolome results.
Overall Survival [From the day of transplant (Day 0) to 2 years posttransplant.]
Comparison of overall survival between obtained groups according to metabolome results.
Disease free survival [From the day of transplant (Day 0) to 2 years posttransplant.]
Comparison of overall survival between obtained groups according to metabolome results.

Secondary Outcome Measures

Microbiome (alpha diversity of the intestinal microbiota) [At Day -15 and Day +30 post-transplant.]
Comparison of biological alpha diversity of the intestinal microbiota. Calculation of alpha diversity (Shannon's diversity index, observed OTUs, Faith's Phylogenetic Diversity and Evenness) index by QIIME-
Microbiome (beta diversity of the intestinal microbiota) [At Day -15 and Day +30 post-transplant.]
Comparison of biological beta diversity of the intestinal microbiota. Calculation of beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFrac distance and Unweighted UniFrac distance) index by QIIME-
Microbiome (alpha diversity of the plasmatic microbiota) [At Day -15 and Day +30 post-transplant.]
Comparison of biological alpha diversity of the plasmatic microbiota. Calculation of alpha diversity (Shannon's diversity index, observed OTUs, Faith's Phylogenetic Diversity and Evenness) index by QIIME-
Microbiome (beta diversity of the plasmatic microbiota) [At Day -15 and Day +30 post-transplant.]
Comparison of biological beta diversity of the plasmatic microbiota. Calculation of beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFrac distance and Unweighted UniFrac distance) index by QIIME-
Relapse [From the day of transplant (Day 0) to +30, +100, +365 and two years posttransplant.]
Comparison of patients´s incidence of relapse of the malignant disease between the groups obtained according to microbiome-metabolome results.
Mortality [From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant.]
Comparison of patients mortality between the groups obtained according to microbiome-metabolome results.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Patients Patients receiving an allotransplant at participating hospitals during the study period before initiating conditioning period.

Inclusion Criteria:

Patients of any age who will receive allogeneic hematopoietic transplantation of any modality with any diagnosis.
Agreement of the patient to participate by signing the informed consent or his/her legal representatives/assent (if applicable).

Exclusion Criteria

Allotransplant recipients in stages after the initial pre-conditioning.

Donors

Family donors from patients included in the study:

Inclusion criteria:

Agreement of the donor to participate by signing the informed consent or his/her legal representatives/assent (if applicable).
Donor relatives with any degree of identity in the Human Leukocyte Antigens (HLA).

Exclusion Criteria:

Unrelated donors
Transplants from umbilical cord blood source.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital Universitario Virgen del Rocío, Sevilla	Sevilla	Seville	Spain
2	Hospital Universitario Reina Sofía	Córdoba		Spain
3	Hospital Virgen de las Nieves de Granada	Granada		Spain
4	Hospital del Niño Jesús, Madrid	Madrid		Spain
5	Hospital La Paz, Madrid	Madrid		Spain
6	Hospital Regional Universitario de Málaga	Málaga		Spain
7	Hospital Clínico de Salamanca	Salamanca		Spain
8	Hospital Marqués de Valdecillas, Santander	Santander		Spain
9	Hospital Clínico de Valencia	Valencia		Spain

Sponsors and Collaborators

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Instituto de Salud Carlos III

Investigators

Principal Investigator: Ildefonso Espigado, PhD, Seville University, Dep. of Medicine. Virgen del Rocío/Virgen Macarena Hospitals, Instituto de Investigación Biomédica de Sevilla / CSIC, Seville, Spain