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

Graft-versus-host Disease Clinical Trial

— AlloBolome  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05186857
• Other study ID #: AlloBolome
• Status: Active, not recruiting
• Start date: January 23, 2023
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft-versus-host Disease

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Virgen de las Nieves de Granada	Granada
Spain	Hospital del Niño Jesús, Madrid	Madrid
Spain	Hospital La Paz, Madrid	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Marqués de Valdecillas, Santander	Santander
Spain	Hospital Universitario Virgen del Rocío, Sevilla	Sevilla	Seville
Spain	Hospital Clínico de Valencia	Valencia

Sponsors (2)

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

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolome	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).	From pre-Conditioning (Day -15) to Day +100 post-transplant.
Primary	Incidence of Acute graft versus host disease	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.	From the day of transplant (Day 0) to Day +100 posttransplant.
Primary	Overall Survival	Comparison of overall survival between obtained groups according to metabolome results.	From the day of transplant (Day 0) to 2 years posttransplant.
Primary	Disease free survival	Comparison of overall survival between obtained groups according to metabolome results.	From the day of transplant (Day 0) to 2 years posttransplant.
Secondary	Microbiome (alpha diversity of the intestinal microbiota)	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-	At Day -15 and Day +30 post-transplant.
Secondary	Microbiome (beta diversity of the intestinal microbiota)	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-	At Day -15 and Day +30 post-transplant.
Secondary	Microbiome (alpha diversity of the plasmatic microbiota)	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-	At Day -15 and Day +30 post-transplant.
Secondary	Microbiome (beta diversity of the plasmatic microbiota)	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-	At Day -15 and Day +30 post-transplant.
Secondary	Relapse	Comparison of patients´s incidence of relapse of the malignant disease between the groups obtained according to microbiome-metabolome results.	From the day of transplant (Day 0) to +30, +100, +365 and two years posttransplant.
Secondary	Mortality	Comparison of patients mortality between the groups obtained according to microbiome-metabolome results.	From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant.