Changes in the Gut Microbiota of Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT) (COLLECT)

Changes Over Time in the Gut Microbiota of High-risk Hematological Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)

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.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation; Stem Cell Transplant Complications; Graft-versus-host-disease

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)

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Maria Vehreschild, MD; Phone Number: +49 221 478 88794; Email: maria.vehreschild@uk-koeln.de

Study Locations

• Germany
  • Cologne, Germany, 50937
    • Recruiting
    • University Hospital of Cologne
    • Contact: Maria Vehreschild, MD; Phone Number: +49 221 478 88794; Email: maria.vehreschild@uk-koeln.de

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

university hospital cologne

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Admitted for allogeneic HSCT; Patients admitted for performance of an allogeneic HSCT after high dosis chemotherapy.
First diagnosis AML; Patients admitted with a first diagnosis of an acute myeloid leukemia for chemotherapy. Depending on factors like age or molecular risk profile some of these patients will proceed to allogeneic HSCT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the association between changes in the intestinal microbiota and the incidence of gastrointestinal GvHD	Analyse changes over time in the intestinal microbiota using 16S ribosomal ribonucleic acid (rRNA) analysis and assess microbiota diversity.	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the association between changes in the intestinal microbiota and the incidence of non-relapse mortality	Analyse changes over time in the intestinal microbiota using 16S rRNA analysis and assess microbiota diversity.	365 days
Investigation of the influence of antibiotics and other risk factors on microbiota changes within this cohort	Analyse changes over time in the intestinal microbiota using 16S rRNA analysis and assess microbiota diversity.	365 days
Analysis of the association of 3-indoxylsulfate 3-IS in urine/blood with observed microbiota changes	3-indoxylsulfate (3-IS) concentration levels will be quantified using liquid chromatography in combination with mass spectrometry.	365 days
Assessment of the effect of microbiota dysbiosis on cytokine and lymphocyte profiles	Cytokine analysis will be performed on the collected plasma samples (citrate) using multiplex assays and read on a Luminex100™ platform.	365 days

Collaborators and Investigators

• Sponsor: University of Cologne
• Investigators: Principal Investigator: Maria Vehreschild, MD, University Hospital of Cologne, Department of Internal Medicine / Infectious Diseases, Cologne, Germany

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Graft-versus-host-disease; Allogeneic hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Graft vs Host Disease
• Other Study ID Numbers: COLLECT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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