PBMC as Biomarkers of Diabetic Cardiomyopathy

Type 2 Diabetes Clinical Trial

— MOBI  

Official title:

Use of Peripheral Blood Mononuclear Cells as biOmarkers of diaBetic cardIomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05651919
• Other study ID #: 69HCL22_0580
• Secondary ID: 2022-A02435-38
• Status: Recruiting
• Start date: May 23, 2023
• Est. completion date: February 23, 2025

Study information

• Verified date: May 2024
• Source: Hospices Civils de Lyon
• Contact: Hélène THIBAULT, PU,PH
• Phone: 0427856691
• Email: Helene.thibault[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Type 2 diabetes (T2D), especially when associated with metabolic syndrome (MS) is at high risk to develop heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF), and the specific impact of T2D+MS in cardiac function impairment is usually known as "diabetic cardiomyopathy" (DC). Cardiac remodelling (ie hypertrophy) and subtle myocardial dysfunction are highly prevalent in T2D+MS but not specific enough to predict further HFpEF or HFmrEF. Also, current biomarkers can identify but do not predict HFpEF or HFmrEF in T2D patients; Furthermore, specific biomarkers are needed. Peripheral blood mononuclear cells (PBMC) obtained from a peripheral blood sample can provide insights from calcic and inflammatory pathways, and may identify more specific molecular signatures shared between T2D+MS and HFpEF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 23, 2025
• Est. primary completion date: February 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

Inclusion criteria common to the 4 groups:

• Patient coming for a scheduled cardiology or endocrinology visit as part of their follow-up

• Patient coming on an empty stomach for the blood test

• Male or female aged between 40 and 80 inclusive

• Patient without systemic disease and/or without anti-inflammatory treatment

• Patient not objecting to this research

• Patient accepting the conservation of biological samples and the performance of genetic analyzes

Group 1: No-T2D +MS / No-HF (control group)

• Patient without T2D or MS and without heart failure coming to a consultation or day hospital for another reason (e.g. screening for atypical symptom, etc.)

Group 2: No-T2D +MS / HFpEF or HFmrEF

• Patient without T2D or MS

• HFpEF or HFmrEF. diagnosed

Group 3: T2D+MS / no-HF

• Patient diagnosed with T2D+MS

Group 4: T2D +MS / HFpEF or HFmrEF

• Patient diagnosed with T2D and MS

• HFpEF or HFmrEF. diagnosed

Exclusion Criteria:

Non-inclusion criteria common to the 4 groups:

• History (ATCD) of cardiovascular disease (valvular (more than moderate valve disease), radiation, post-cardiotoxic chemotherapy, amyloidosis, etc.) other than HFpEF or HFmrEF

• Atrial fibrillation or permanent flutter

• Systemic disease and/or anti-inflammatory treatment

• ATCD of known coronary artery disease

• Unbalanced hypertension (>160/100 mmHg)

• Pregnant and lactating women on questioning

• Persons deprived of their liberty by a judicial or administrative decision

• Persons subject to psychiatric care

• Patients subject to a legal protection measure (guardianship, curators)

• Subject participating in another interventional research including a period of exclusion still in progress.

• Chronic kidney disease(GFR<30ml/min/1.73m2)

Group 1: No-T2D +MS / No-HF (control group)

• Presence of diabetes (whatever the type) and MS

• Presence of heart failure or other known heart disease

Group 2: No-T2D +MS / HFpEF or HFmrEF

• Presence of diabetes (whatever the type) and MS

• No Heart failure

• Left Ventricular Ejection Fraction (LVEF) on ultrasound = 40%

Group 3: T2D+MS / no-HF

• Without diabetes or other type of diabetes than T2D

• Presence of Heart failure or other known coronary artery disease

Group 4: T2D +MS / HFpEF or HFmrEF

• Absence of diabetes or presence of another type of diabetes than T2D

• Absence of Heart failure

• LVEF on ultrasound = 40%

Related Conditions & MeSH terms

• Cardiomyopathies
• Diabetes Mellitus, Type 2
• Diabetic Cardiomyopathies
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Metabolic Syndrome
• Type 2 Diabetes

Intervention

Biological:
• Blood test
During the routine blood test of the patient, 4 more tubes of 4 milliliters (mL) will be collected to make a biological collection of PBMC and plasma for further analysis.

Behavioral:
• quality of life Questionnaire
During the routine medical visit, the patient will be asked to fill in a short questionnaire about quality of life. This is a descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. This decision results into a 1-digit number that expresses the level selected for that dimension. Each patient's health state is referred to in terms of a 5-digit code; Levels of perceived problems are coded as follows: Level 1 is coded as a '1' (indicating no problem) Level 2 is coded as a '2' (indicating some problems) Level 3 is coded as a '3' (indicating extreme problems) For example, state 11223 indicates no problems with mobility and self-care, no problems with performing usual activities, moderate pain or discomfort and extreme anxiety or depression, while state 11111 indicates no problems.
• Diet habits questionnaire
During the routine medical visit, the patient will be asked to fill in a short questionnaire about his diet habits. This is an exploratory questionnaire that describes and quantifies the foods (pro- or anti-inflammatory) ingested by patients.

Locations

Country	Name	City	State
France	Hopital Louis Pradel	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Initial level of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF	The calcic profile of PBMC will be quantified by flow cytometry to determine the values of the kinetics parameters of Ca2+ fluxes (initial level).	Day of blood sample (inclusion visit)
Primary	Comparison of amplitude of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF	The calcic profile of PBMC will be quantified by flow cytometry to determine the values of the kinetics parameters of Ca2+ fluxes (amplitude).	Day of blood sample (inclusion visit)
Primary	Comparison of area under curve of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF	The calcic profile will be quantified by flow cytometry to determine the values of the kinetics parameters of Ca2+ fluxes (area under curve).	Day of blood sample (inclusion visit)
Primary	Comparison of slope of the response to pharmacological stimulation of Ca2+ fluxes from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF	The calcic profile of PBMC will be quantified by flow cytometry to determine the values of the kinetics parameters of Ca2+ fluxes (slope of the response to pharmacological stimulation).	Day of blood sample (inclusion visit)
Primary	Comparison of the inflammatory profile of PBMC from T2D+MS patients vs non T2D+MS patients, according to the presence or not of HFpEF or HFmrEF	The inflammatory profile will evaluate by flow cytometry the proportion of the different populations of monocytes and lymphocytes using several labeling antibodies.	Day of blood sample (inclusion visit)