Investigation of the Gut Microbiota in Patients With Acute Myeloid Leukemia

Not Applicable

Completed

• Conditions: Cachexia; Acute Myeloid Leukemia
• Interventions: Other: collection of clinical data and biological samples

• Registration Number: NCT03881826
• Lead Sponsor: Université Catholique de Louvain

Brief Summary

This cohort study aims to investigate the composition and activity of the gut microbiota of patients newly diagnosed for acute myeloid leukemia (AML), in relationship with their food habits and cachectic hallmarks. The recruitment for this study is currently ongoing with the help of clinicians, nurses and data managers at the Saint-Luc clinics, University Hospital Leuven (Campus Gasthuisberg) and University Hospital Gent.

Primary Objective

•To assess the composition and activity of the gut microbiota in patients with acute myeloid leukemia (AML) compared to matched control subjects.

Secondary Objectives

* To investigate correlations between the gut microbiota, cachectic hallmarks and gut microbiota-related markers in the blood (gut permeability markers, microbial compounds, microbial metabolites).

* To characterize the changes in the gut microbial ecosystem that are induced by chemotherapy and associated with colitis.

* To assess whether the composition of the gut microbiota can predict the severity of chemotherapy-related colitis.

Study Design

This is an academic multi-centric prospective study. The study is composed of two cohorts (Fig. 1). In Cohort A, patients are included before any chemotherapy. Biological samples (urine, feces, blood) are collected, alongside information on nutritional habits, appetite and medical records. Muscle strength and body composition are also measured. Only patients receiving a standard chemotherapy are included in Cohort B. In Cohort B, biological samples are collected and body composition, muscle strength and appetite are evaluated at 2 different time points, at the end of the chemotherapy (T1) and at discharge (T4).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-04
• Study First Submitted: 2019-02-05
• Study First Submitted QC: 2019-03-18
• Study First Posted: 2019-03-20
• Primary Completion: 2020-01-11
• Study Completion: 2020-11-10
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-21
• Last Update Posted: 2021-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patients with

  • A diagnosis of AML and related precursor neoplasms according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML)
  • Acute leukemia's of ambiguous lineage according to WHO 2008
  • A diagnosis of refractory anemia with excess of blasts (MDS REAB) 2 and IPSS (International Prognostic Scoring System)-R score > 2.

• World Health Organization performance status 0, 1 or 2

• Sampled bone marrow and/ blood cells at diagnosis with molecular analysis.

• Written informed consent

• Good command of the French or Dutch language

Exclusion Criteria

• Age < 18 years
• Age > 75 years
• Pregnancy
• Antibiotics consumption during the last 30 days before inclusion
• Recent chemotherapy (< 3 months), with exclusion of hydroxyurea
• BMI >30
• Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance)
• Gastric bypass
• Current treatment with antidiabetic or hypoglycemic drugs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	collection of clinical data and biological samples	-
Haematological patients	collection of clinical data and biological samples	-

Primary Outcome Measures

Name	Time	Method
Description of gut microbiota composition in patients with acute myeloid leukemia and control subjects	Day 0 i.e.: feces sampling is done at time of diagnosis before any chemotherapy	Sequencing DNA extracts from patients' feces (both patients with acute myeloid leukemia and control subjects matched for BMI, sex and age) to obtain the description of gut microbiota composition in those patients
Measure of metabolites production by the gut microbiota in patients with acute myeloid leukemia and control subjects	Day 0 i.e.: feces sampling is done at time of diagnosis before any chemotherapy	1H-NMR metabolomics performed on patients' feces (both patients with acute myeloid leukemia and control subjects matched for BMI, sex and age) to report the metabolites produced by the gut microbiota of those patients

Secondary Outcome Measures

Name	Time	Method
Changes in body composition	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	Measure of body composition by bio-electric impedance (in kg)
Changes in appetite	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	Measure of appetite with the SNAQ questionnaire (score from 5 to 20)
Changes in muscle strength	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	Measure of muscle strength with Jamar dynamometer (in kg)
Changes in gut microbiota-related markers in the blood (gut permeability markers and microbial compounds)	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	ELISA (in pg/ml)
Changes in gut microbiota-related markers in the blood (microbial metabolites)	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	1H-NMR metabolomics
Changes in gut microbiota-related markers in urine (gut permeability markers, microbial compounds, microbial metabolites)	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	ELISA and 1H-NMR metabolomics
Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after chemotherapy	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	Sequencing DNA extracts from patients' feces to obtain the description of gut microbiota composition in those patients.
Changes in metabolites production by the gut microbiota in patients with acute myeloid leukemia before, during and after chemotherapy.	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	1H-NMR metabolomics performed on patients' feces to report the metabolites produced by the gut microbiota of those patients.
Changes in number of participants with treatment related-related adverse events as assessed by CTCAE v4.0	at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy);	CTCAE (common terminology criteria for adverse event version 4)

Trial Locations

Locations (1)

UCLouvain; 🇧🇪 Brussels, Belgium