GLUTADIAB: Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT04353869

Collaborator

National Research Agency, France (Other)

975

Enrollment

Locations

Anticipated Duration (Months)

487.5

Patients Per Site

12.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Experimental data suggest that glutamine catabolism in involved in the activation of macrophages by generating TCA(Tricarboxylic acid) intermediates that promote the pro-inflammatory polarization of macrophages. The project investigates the possible link between glutaminolysis, monocytes polarization and diabetes related cardiovascular complications in humans

Condition or Disease	Intervention/Treatment	Phase
Glutamine Diabetic Cardiovascular Complications	Biological: Bio collection

Detailed Description

The aim of the study is to investigate the role of glutamine metabolism in the pro-inflammatory activation of macrophages in diabetes and related cardiovascular complications.

The study focuses on 3 adult patients' population with different diabetic status and level of cardiovascular risk:

Patients with uncomplicated type 1 or type 2 diabetes and low cardiovascular risk
Patients with uncomplicated type 1 or type 2 diabetes and high cardiovascular risk
Patients with complicated type 1 or type 2 diabetes

Participants (n=975) will be recruited at clinical sites, in the diabetes and cardiology departments (APHP, Bichat - Claude-Bernard Hospital and APHP, Lariboisière Hospital), over a 2-year period.

The study will consist in a single visit. During a scheduled hospitalization or consultation as part of the follow-up of their diabetes or as part of the follow-up of their cardiological problems, clinical data will be collected as well as additional blood and urine samples for analyses and biobanking. There will be no other intervention specific to the study.

Study Design

Study Type:

Observational

Anticipated Enrollment :

975 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Targeting Glutamine Metabolism to Prevent Diabetic Cardiovascular Complications

Actual Study Start Date :

Nov 16, 2020

Anticipated Primary Completion Date :

Jan 16, 2024

Anticipated Study Completion Date :

Jan 16, 2024

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Patients with uncomplicated diabetes and low cardiovascular risk During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA (Éthylènediaminetétraacétique) tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).	Biological: Bio collection venous blood sampling and collection of urine
Group 2 Patients with uncomplicated diabetes and high cardiovascular risk During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).	Biological: Bio collection venous blood sampling and collection of urine
Group 3 Patients with complicated diabetes During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).	Biological: Bio collection venous blood sampling and collection of urine

Arm

Intervention/Treatment

Group 1

Patients with uncomplicated diabetes and low cardiovascular risk During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA (Éthylènediaminetétraacétique) tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).

Biological: Bio collection

venous blood sampling and collection of urine

Group 2

Patients with uncomplicated diabetes and high cardiovascular risk During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).

Biological: Bio collection

venous blood sampling and collection of urine

Group 3

Patients with complicated diabetes During a scheduled hospitalization or consultation as part of the follow-up of their diabetes additions of biological samples, which include: A unique venous blood sampling of 9 tubes: 4 x 7 mL EDTA tubes + 3 x 5 mL EDTA tubes + 2 x 4 mL no additive tubes (total: 51 mL) at a single time during the study and collection of 2 monovettes of 1.6 ml urine (total: 3.2 mL).

Biological: Bio collection

venous blood sampling and collection of urine

Outcome Measures

Primary Outcome Measures

Compare the plasma concentrations of glutamine in patients with various levels of cardiovascular (CV) risk. [DAY 1]
plasma concentration of glutamine in each subject.

Secondary Outcome Measures

Study glutamine metabolism in patients with various levels of CV risk [DAY 1]
plasma concentration of glutamate in each treatment group
Study glutamine metabolism in patients with various levels of CV risk [DAY1]
plasma concentration of a-ketoglutarate, fumarate, and succinate in each treatment group
Study glutamine metabolism in patients with various levels of CV risk [DAY 1]
monocyte cytoplasmic concentration of a-ketoglutarate, fumarate and succinate in each treatment group
study the inflammatory status in patients with various levels of CV risk [DAY 1]
plasma concentration of VEGF (Vascular endothelial growth factor) in each treatment group
study the inflammatory status in patients with various levels of CV risk [DAY 1]
plasma concentration of the proinflammatory cytokines IL-1, IL-6, IL-8 (interleukin) and TNF-a (Tumor Necrosis Factor alpha)
study the inflammatory status in patients with various levels of CV risk [DAY 1]
blood concentration of circulating PBMCs (peripheral blood mononuclear cell)
study the monocyte activation status in patients with various levels of CV risk [DAY 1]
frequency of monocyte subsets (CD14++CD16+, CD14++CD16++, CD14+CD16++)
characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B (Lysine Demethylase 6B) and TET2 (Ten-eleven-translocation 2) activity in blood monocytes from patients with various levels of CV risk [DAY 1]
Number of transcript for each gene
characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B and TET2 activity in blood monocytes from patients with various levels of CV risk [DAY 1]
Number of methylated gene loci and their proportion of methylation
characterize the transcriptomic program through modification gene expression and epigenetic changes related to KDM6B and TET2 activity in blood monocytes from patients with various levels of CV risk [DAY 1]
Frequency and level of histone H3K27me (Methylation of lysine 27 on histone H3) methylation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria General inclusion criteria applying to the five populations are the following:

Age above 18 years
BMI between 25 and 40 kg/m²

Inclusion criteria according to study group are listed below.

Group 1: Patients with uncomplicated diabetes and low cardiovascular risk, additional inclusion criteria are:

5 or more years of diabetes
6% < HbA1c < 10%
no history of cardiovascular event, diabetic microvascular complications (kidney function normal and albuminuria/creatininuria < 30 mg/g)
Coronary artery calcium score < 100 (assessment < 12 months)

Group 2: Patients with uncomplicated diabetes and high cardiovascular risk, additional inclusion criteria are:

5 or more years of diabetes
6% < HbA1c < 10%
no history of cardiovascular eventand diabetic nephropathy no more than stage 2 (i.e. GFR ≥ 60 ml/min by MDRD or CKD-EPI formula and albuminuria/creatininuria ≤ 30 mg/g)
Coronary artery calcium score > 400 (assessment < 12 months)

Group 3: Patients with complicated diabetes, additional inclusion criteria are:

5 or more years of diabetes
6% < HbA1c < 10%
A history of cardiovascular event (myocardial infarction, stroke, peripheral vascular disease, or angioplasty) at least 3 months ago

Exclusion Criteria:

Solid organ or bone marrow transplant patient
Pregnant or breastfeeding woman
Absence of free and informed consent
Non-affiliation to a social security regimen or CMU (universal health coverage)
Subject deprived of freedom, subject under a legal protective measure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Diabétologie - Hôpital Lariboisière	Paris		France	75010
2	Diabetologie Bichat	Paris		France	75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris
National Research Agency, France

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT04353869

Other Study ID Numbers:

GLUTADIAB

First Posted:

Apr 21, 2020

Last Update Posted:

Jul 11, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Assistance Publique - Hôpitaux de Paris

Diabetes

Cardiovascular complications

Glutamine metabolism

Study Results

No Results Posted as of Jul 11, 2022