Clinical trial NCT05186857: Metabolome and Microbiome Impact on Acute GVHD in Recipients of Hematopoietic Transplant
Official title: Impact of Intestinal Metabolome and Microbiome Disbalance of Recipients of Hematopoietic Transplant in the Development of Acute Graft Versus Host Disease.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Graft-versus-host Disease
Keywords: Acute graft-versus-host disease
Microbiome
Metabolome
Hematopoietic transplant
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2022-01-11
Enrollment: 88
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients receiving an allotransplant and family donors of the included patients.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Metabolome
timeFrame: From pre-Conditioning (Day -15) to Day +100 post-transplant.
measure: Incidence of Acute graft versus host disease
timeFrame: From the day of transplant (Day 0) to Day +100 posttransplant.
measure: Overall Survival
timeFrame: From the day of transplant (Day 0) to 2 years posttransplant.
measure: Disease free survival
timeFrame: From the day of transplant (Day 0) to 2 years posttransplant.
Secondary outcomes:
measure: Microbiome (alpha diversity of the intestinal microbiota)
timeFrame: At Day -15 and Day +30 post-transplant.
measure: Microbiome (beta diversity of the intestinal microbiota)
timeFrame: At Day -15 and Day +30 post-transplant.
measure: Microbiome (alpha diversity of the plasmatic microbiota)
timeFrame: At Day -15 and Day +30 post-transplant.
measure: Microbiome (beta diversity of the plasmatic microbiota)
timeFrame: At Day -15 and Day +30 post-transplant.
measure: Relapse
timeFrame: From the day of transplant (Day 0) to +30, +100, +365 and two years posttransplant.
measure: Mortality
timeFrame: From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant.
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío, Sevilla
state: Seville
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves de Granada
city: Madrid
country: Spain
facility: Hospital del Niño Jesús, Madrid
city: Madrid
country: Spain
facility: Hospital La Paz, Madrid
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Santander
country: Spain
facility: Hospital Marqués de Valdecillas, Santander
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
Study officials:
affiliation: Seville University, Dep. of Medicine. Virgen del Rocío/Virgen Macarena Hospitals, Instituto de Investigación Biomédica de Sevilla / CSIC, Seville, Spain
name: Ildefonso Espigado, PhD
role: PRINCIPAL_INVESTIGATOR
References: