Metabolic Inflexibility of the Heart as a Predictor of Occurrence of Heart Failure in Patients With Type 2 Diabetes (MET-INF-T2D)

In the type 2 diabetic population, some patients are particularly at risk of developing early heart failure. Finding markers to identify these at-risk individuals is therefore an important scientific objective in order to avoid/delay the development of heart failure.

The protocol will be proposed to type 2 diabetic patients hospitalized for insulin therapy upon admission to the diabetology department and healthy volunteers.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Diagnostic test: MRI in patients; Diagnostic test: MRI in healthy volunteers

Detailed Description

The objective of this study is to identify subjects at risk defined by the existence of an alteration in the maximal longitudinal contractility of the left ventricle by measuring myocardial deformation in magnetic resonance imaging (MRI) before (D1) and after (D15±3) an imposed metabolic change (insulin treatment and correction of hyperglycaemia) in a population with type 2 diabetes in primary prevention requiring the start of insulin therapy because of an imbalance in their diabetes (HbA1c ≥ 10%). To do so, patients and healthy volunteers will be matched on sex and age (+/- 5 years).

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zohra ABBOU; Phone Number: +33(0)1.42.16.16.25; Email: zohra.abbou@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Hopital Pitie-Salpetriere

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients

• Patient aged over 18 and under 75
• Type 2 diabetes treated with bitherapy for at least 6 months
• Unbalanced diabetes (HbA1c ≥ 10%)
• Indication for insulin therapy (introduction of a slow-acting insulin injection per day or adding rapid-acting insulins before meals in the event of a slow-acting or semi-acting insulin injection already present on admission)
• BMI < 40 kg/m2
• Cardiovascular examination without clinically significant abnormality
• LVEF > 50% (measured by echocardiography)
• Free from any acute intercurrent pathology for more than 10 days,
• Accept the constraints of the protocol and sign the informed and free consent
• Be affiliated to a French social security scheme or entitled

Healthy volunteers

• Be over 18 and under 75
• Have a BMI < 30 kg/m²
• Be asymptomatic
• Normal clinical examination
• Normal resting 12-lead ECG
• Normal biological balance (fasting blood glucose, HBA1c, ionogram, creatinine, NFS, BNP / pro-BNP, troponin)
• Accept the constraints of the protocol and sign the informed and free consent
• Be affiliated to a French social security scheme or entitled

Exclusion Criteria:

Patients

• Current or recent infections (< 10 days)
• Neoplastic disorders (except carcinoma in situ of the cervix or cutaneous epithelioma), haematological, cardiovascular (except controlled arterial hypertension), psychiatric, neurological, chronic respiratory failure
• Presence of renal insufficiency defined as an estimated glomerular filtration rate < 30mL/min/1.73m2 according to the MDRD formula
• Rhythm and/or conduction disorder not previously known and discovered during the 12-lead ECG performed at inclusion
• Known cardiovascular pathology (arteriopathy and/or cardiomyopathy)
• Contraindications to MRI with injection of gadolinium: claustrophobia, pacemaker, metallic foreign body, anxiety attack, nausea, vomiting, panic attack, vertigo, malaise without traumatic consequences, allergy to contrast products, renal failure defined by an estimated glomerular filtration rate < 30mL/min/1.73m2 according to the MDRD formula, diffusion of the contrast product during its infusion
• Contraindication for regadenoson injection: hypersensitivity to the active substance or to any of the excipients, second or third degree atrioventricular (AV) block or sinoatrial node dysfunction, unless these patients are carriers an operational pacemaker, unstable angina not stabilized by medical treatment, severe hypotension, decompensated heart failure
• Pregnant or breastfeeding women
• Persons deprived of their liberty by judicial decision or benefiting from legal protection (under guardianship or curatorship)
• Abuse of alcohol or narcotics
• Patient under AME (state medical aid)
• Participation in another interventional research involving the human person or being in the exclusion period at the end of a previous research involving the human person

Healthy volunteers

• Contraindications to MRI: claustrophobia, metallic foreign body, anxiety attack, nausea, vomiting, panic attack, vertigo, malaise without traumatic consequences
• Have kidney disease with GFR < 30 mL/min
• Known cardiac pathology
• Personal cardiovascular history
• Primary cardiomyopathy or familial congenital heart disease
• Being deprived of liberty or under legal protection (under guardianship or curatorship)
• Witness under AME (state medical aid)
• Participation in another interventional research involving the human person or being in the exclusion period at the end of a previous research involving the human person
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Patients with insulinotherapy introduction; Injected MRI	Diagnostic test: MRI in patients; Injected MRI
SHAM_COMPARATOR: Healthy volunteers; No injected MRI	Diagnostic test: MRI in healthy volunteers; non injected MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular myocardial longitudinal strain measured by MRI (%)	Myocardial longitudinal strain measured by dynamic MRI images (%) throughtout feature tracking strategy	15 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Left ventricular myocardial radial strain measured by dynamic MRI images (%) throughtout feature tracking strategy	15 days
Extracellualar volume (%) and collagene fraction (%) measured from MRI images	15 days
Rest ratio in myocardial perfusion reserve calculated from rest and stress MRI images	15 days
Measurement of early and late filling wave velocities (E, A) and myocardial longitudinal velocity (E')	15 days
Myocardial triglycerides fraction measured from proton MR spectroscopy	15 days
Epicardial fat volume measured from ECG gated Dixon MRI images	15 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Fabrizio ANDREELLI, MD PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2022
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): October 1, 2023

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (ACTUAL): August 1, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: diabetes; insulin therapy; metabolic inflexibility
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Heart Failure; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: APHP190632

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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