Clinical trial NCT04303364: CARdiomyopathy in Type 2 DIAbetes Mellitus
Official title: CARdiomyopathy in Type 2 DIAbetes Mellitus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiomyopathy, Diabetic
Keywords: Type2 Diabetes Mellitus
Heart Failure with preserved ejection fraction
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Consorcio Centro de Investigación Biomédica en Red (CIBER)
First posted: 2020-03-11
Enrollment: 1600
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Since CARDIATEAM aims to assess the uniqueness of DCM, it will include a group of non-diabetic non-HFpEF individuals with diversified characteristics relating to obesity, glucose intolerance and hypertension. Consequently, CARDIATEAM cohort will recruit both non-diabetic and diabetic patients with a large spectrum of demographic, metabolic and cardiac (heart failure vs. no heart failure) clinical data.

Brief summary: The objective of the CARDIATEAM clinical study is to assess the uniqueness of diabetic cardiomyopathy (DCM) relative to other forms of cardiomyopathy using unsupervised clustering approaches based on deep phenotyping (clinical, imaging and biological) information.

Detailed description: CARDIATEAM study will address the uniqueness of DCM, and its progression towards heart failure (HF) with preserved ejection fraction (HFpEF) by recruiting a prospective CARDIATEAM cohort (n=1600 individuals) from existing cohorts using a defined set of selection criteria and will include type2-Diabetes mellitus (T2DM)and non-diabetic patients with a large spectrum of demographic, metabolic and cardiac clinical data. This will yield a wide range of T2DM - related phenotypes including common confounders such as BMI, smoking, age and blood pressure.

To clarify the phenotype of DCM and to differentiate it from the other forms of HF such as HFpEF or HCM, CARDIATEAM will perform unbiased clustering analysis from an in-depth phenotyping of these patients' populations

Eligibility criteria: Inclusion criteria

* Female or male, aged between ≥ 40 and ≤80 years
* Normal LVEF AND absence of akinetic segment assessed by echocardiography (i.e. LVEF≥50%)
* Patients diagnosed according to the specific diagnostic criteria of each disease (Cf. table below (definition criteria)). For each group, the diagnosis will be based on current accepted criteria:

  * HFpEF: left ventricular ejection fraction (LVEF) LVEF≥50% AND presence/or history of symptoms (e.g. breathlessness, ankle swelling and fatigue) or signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) of heart failure AND significant diastolic dysfunction (left atrial volume index \>34 mL/m2 or a LVMI ≥115 g/m2 for males and ≥95 g/m2 for female, E/e' ≥13 and e' \<9 cm/s) OR NT-proBNP \>125 pg/Ml
  * No HFpEF: LVEF≥50% AND absence of symptoms (e.g. breathlessness, ankle swelling and fatigue) or signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) of heart failure
  * T2DM: HbA1c ≥ 6.5% (≥ 48 mmol/L) AND Fasting Plasma Glucose ≥7.0 mmol/L (≥126 mg/dL) or anti-diabetic treatment
  * Non T2DM: HbA1c \< 6.5% AND Fasting Plasma Glucose \<7.0 mmol/L without any anti-diabetic treatment including normoglycemic subjects
  * HCM: patients with non-obstructive HCM of sarcomeric cause (proven with common genetic cause) and with LV wall thickness ≥ 15 mm in one or more myocardial segments in the absence of abnormal afterload conditions.
* Suitable echocardiographic window
* Absence of history of coronary artery disease including history of myocardial ischaemia, myocardial infarction or percutaneous coronary intervention
* Absence of significant coronary artery disease (CAD) defined as:

  * the absence of coronary artery stenosis ≥50% on a cardiac computed tomography (CT) OR a coronary angiography OR normal Fractional Flow Reserve (FFR \>0.80) OR
  * Coronary Artery Calcium score (CAC) \<100 performed within the 48 months before inclusion
* Patient covered by a health insurance

Non-inclusion criteria:

* Diabetes mellitus other than type 2 (type 1, LADA, MODY, NODAT, etc.)
* Suboptimal echocardiographic window
* Significant valvular heart disease defined as severe aortic regurgitation or severe primary mitral regurgitation or aortic stenosis with a peak transvalvular velocity ≥3m/s or mitral stenosis with a mitral valve area \< 1.5cm²
* Chronic atrial fibrillation or any significant arrhythmia at inclusion
* Renal insufficiency defined as eGFR\<30 mL/min/1.73m²
* History of and candidate to bariatric surgery
* Obstructive hypertrophic cardiomyopathy (definition: maximal gradient at rest \<30 mmHg)
* Hypertrophic cardiomyopathy due to a non-sarcomeric etiology, i.e. known infiltrative or storage disorder mimicking HCM such as Fabry disease or amyloidosis
* Life threatening comorbidities (i.e. history of or active cancer treated with chemotherapy or radiotherapy, end-stage heart failure, severe lung disease, cirrhosis)
* Pregnancy/Lactating mother
* Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol
* Inability to understand the local language
* Individuals deprived of liberty
* Protected persons (under guardianship or curatorship)
* Contra-indication to CMR (please see CMR-SOP):
* Known hypersensitivity to gadolinium based product (including gadoteric acid and meglumine)
* Known COVID-19 symptomatic infection requiring hospitalization

Primary outcomes:
measure: Assess the uniqueness of diabetic cardiomyopathy (DCM) relative to other forms of cardiomyopathy
timeFrame: 3 years
Secondary outcomes:
measure: Identify the best clinical, biological, imaging and multi-OMICs predictors belonging to each identified cluster
timeFrame: 4 years
measure: Assess prospective health outcomes (i.e. overall mortality, cardiovascular events and cardiac function) in the diabetic cardiomyopathy cluster identified
timeFrame: 5 years
measure: Explore the pathophysiological and potentially causal pathways characterizing diabetic cardiomyopathy
timeFrame: 5 years
Other outcomes:
Locations:
city: Bron
country: France
facility: Hopital Louis Pradel
city: Créteil
country: France
facility: Cardiology Outpatient Department at Hôpital Henri Mondor.
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
city: Marseille
country: France
facility: department of diabetology and nutrition, APHM
city: Nantes
country: France
facility: Hôpital CHU- Nantes
city: Paris
country: France
facility: Diabetology department, Cochin Institute
city: Paris
country: France
facility: Diabetology departement, Lariboisière Hospital
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG), Cardiology/Cardio Research
city: Maastricht
country: Netherlands
facility: Academisch ziekenhuis Maastricht, Cardiology
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Cardiology (DHL)
city: Barcelona
country: Spain
facility: Hospital Vall Hebrón
city: Barcelona
country: Spain
facility: Institut D'Investigacions Biomedica August Pi I Sunyer (IDIBAPS)
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Dundee
country: United Kingdom
facility: University of Dundee, Div of Molecular&Clinical Medicine
Study officials:
affiliation: Henri Mondor University Hospital
name: Geneviève DERUMEAUX, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: