Clinical trial NCT03148197: Changes in the Gut Microbiota of Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)
Official title: Changes Over Time in the Gut Microbiota of High-risk Hematological Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia
Graft-versus-host-disease
Allogeneic Hematopoietic Stem Cell Transplantation
Stem Cell Transplant Complications
Keywords: Allogeneic hematopoietic stem cell transplantation
Graft-versus-host-disease
Acute Myeloid Leukemia
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2017-05-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: university hospital cologne

Brief summary: COLLECT is a monocentric, prospective, observational study, which aims to assess the association between changes in the intestinal microbiota and the incidence of gastrointestinal graft-versus-host diseases (GvHD). Patients admitted for performance of an allogeneic hematopoietic stem cell transplantation (HSCT) or patients with a first diagnosis of an acute myeloid leukemia (AML) will be enrolled and stool samples will be analyzed using next-generation sequencing. In addition to stool, blood and urine samples will be collected for cytokine and 3-indoxylsulfate analysis.

Exposure to drugs will not be influenced and remains at the discretion of the treating physician.

Detailed description: Documentation of patient is performed by using the web-based survey platform www.ClinicalSurveys.net which was set up by researchers of the University Hospital of Cologne. This survey platform enables an optimal performance in epidemiological, observational, and interventional trials and is characterized by layered access security and frequent data backup. It has been used for numerous registry and cohort studies with approval of competent authorities and ethics boards.

The following data items of patients with a written informed consent are prospectively documented into our database:

* Demographics
* Chemotherapeutic agents
* Other immunosuppressives
* Radiation treatment
* Antibiotic prophylaxis and treatment
* Bowel movement abnormalities
* HSCT Donor and recipient information
* Status of hematological disease
* Days with neutropenia
* Fever and infectious complications

The following samples of patients with a written informed consent are prospectively collected, stored and analyzed:

* Stool samples (16S rRNA analysis)
* Urine (3-IS analysis)
* Ethylenediaminetetraacetic acid (EDTA) blood samples (PBMCs Fluorescence-activated cell sorting (FACS) analysis)
* Citrate blood samples (cytokine analysis)

Eligibility criteria: Inclusion Criteria:

* Age of at least 18 years
* Patients admitted for performance of an allogeneic HSCT OR
* Patients with a first diagnosis of an acute myeloid leukemia
* No contraindication for an allogeneic stem cell transplantation
* Subject is not legally incapacitated
* Written informed consent from the study subject has been obtained

Exclusion Criteria:

* Active inflammatory bowel disease
* Ongoing gastroenteritis at the time of inclusion
* Patient has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the patient participating in the study, would make it unlikely for the patient to complete the study, or would confound the results of the study
* Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
* Persons held in an institution by legal or official order

Primary outcomes:
measure: Assessment of the association between changes in the intestinal microbiota and the incidence of gastrointestinal GvHD
timeFrame: 365 days
Secondary outcomes:
measure: Assessment of the association between changes in the intestinal microbiota and the incidence of non-relapse mortality
timeFrame: 365 days
measure: Investigation of the influence of antibiotics and other risk factors on microbiota changes within this cohort
timeFrame: 365 days
measure: Analysis of the association of 3-indoxylsulfate 3-IS in urine/blood with observed microbiota changes
timeFrame: 365 days
measure: Assessment of the effect of microbiota dysbiosis on cytokine and lymphocyte profiles
timeFrame: 365 days
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital of Cologne
Study officials:
affiliation: University Hospital of Cologne, Department of Internal Medicine / Infectious Diseases, Cologne, Germany
name: Maria Vehreschild, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, No D, Gobourne A, Viale A, Dahi PB, Ponce DM, Barker JN, Giralt S, van den Brink M, Pamer EG. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014 Aug 14;124(7):1174-82. doi: 10.1182/blood-2014-02-554725. Epub 2014 Jun 17.
citation: Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales MA, Giralt SA, Pamer EG, van den Brink MR. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2015 Aug;21(8):1373-83. doi: 10.1016/j.bbmt.2015.04.016. Epub 2015 May 11.
citation: Weber D, Oefner PJ, Hiergeist A, Koestler J, Gessner A, Weber M, Hahn J, Wolff D, Stammler F, Spang R, Herr W, Dettmer K, Holler E. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood. 2015 Oct 1;126(14):1723-8. doi: 10.1182/blood-2015-04-638858. Epub 2015 Jul 24.