Clinical trial NCT02851745: Effects of Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry
Official title: Effects of the Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Left Ventricular Systolic Dysfunction
Lead sponsor: Heart Care Foundation
Sponsor class: OTHER
Collaborators: name: Fondazione dell'Associazione Medici Diabetologi
First posted: 2016-08-02
Enrollment: 188
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the effect of linagliptin 5 mg daily versus the corresponding placebo on the LV systolic function (measured by midwall shortening analysis) in patients with T2DM and a documented baseline concentric LV geometry and LV systolic dysfunction.

Detailed description: Multicentre, randomized, double blind, parallel group comparison of an DPP-4 inhibitor, linagliptin 5 mg od, versus placebo (1:1) in patients with T2DM and a documented baseline concentric LV geometry and LV systolic dysfunction.

The management of glycemia will be left to the Investigator's judgment informed by clinical guidelines. The Investigator will therefore be allowed to undertake appropriate action, i.e.:

* Adjust the background antidiabetic treatment.
* Prescribe an additional antidiabetic medication according to its labeling (with the exclusion of other DPP-4 inhibitor or GLP-1 receptor agonist).

The enrollment period will last 12 months. The patients will be followed up for 48 weeks from randomization.

After the randomization the patients will have a control visit after 2 weeks (Visit 3) and at 3 months from randomization (Visit 4, week 12). At Visit 4 blood samples will be collected.

Afterwards the patients will have one control visit at 24 weeks from randomization (Visit 5) and a final visit at 48 weeks from randomization (Visit 6) with echocardiogram and ECG performed and blood samples collected.

Patients still on study treatment at the time of final visit (Visit 6) will have a post treatment safety follow up (clinical visit or phone contact) 30 days after the study treatment discontinuation.

Eligibility criteria: Inclusion Criteria:

* Men and women aged equal to or more than 40 years at screening.
* Patients with history of T2DM lasting at least six month prior to the screening visit.
* HbA1c ≤ 8.0% (≤ 64 mmol/mol) at screening.
* Evidence of sinus rhythm at screening ECG evaluation
* No clinical signs/symptoms of a cardiac disease and no evidence of coronary artery disease on the basis of clinical, electrocardiographic and echocardiographic evaluation at screening.
* Evidence at baseline echocardiographic examination of concentric left ventricular geometry, defined as relative wall thickness ≥ 0.42. Relative wall thickness was calculated as the end-diastolic ratio 2\* posterior wall thickness/LV diameter.
* Evidence at baseline echocardiographic examination of LV systolic dysfunction defined as Midwall shortening (MFS) ≤15%
* Obtained informed consent

Exclusion Criteria:

* Patients with a confirmed indication for an incretin treatment
* Uncontrolled diabetes: HbA1c \>8.0% (\> 64 mmol/mol) or Fasting Plasma Glucose \> 300 mg/dL measured at screening visit.
* Glitazones within the last three months
* Permanent atrial fibrillation
* Uncontrolled hypertension (defined as systolic blood pressure\>160 and/or diastolic blood pressure \>90)
* Unstable dosage and changes in type of antihypertensive, lipid lowering and antidiabetic drugs within 4 weeks before the screening visit.
* Severe chronic renal dysfunction (defined as estimated glomerular filtration rate \< 30 ml/min/1.73 m2).
* Previous or current documented history of untreated (by using CPAP) obstructive sleep apnea syndrome
* Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis.
* Previous or current documented history of malignant disease
* Pregnancy and breast feeding
* Documented alcohol and drug abuse
* Anticipated poor compliance
* Current participation in a clinical trial with other investigational products

Primary outcomes:
measure: Increase in LV systolic function
timeFrame: 48 weeks
Secondary outcomes:
measure: Changes in diastolic LV function
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
state: BG
city: Catania
country: Italy
facility: P.O. Garibaldi-Nesima
state: CT
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo Della Sofferenza
state: FG
city: Genova
country: Italy
facility: Ospedale Villa Scassi
state: GE
city: Rapallo
country: Italy
facility: Iclas-Istituto Clinico Ligure Alta Spec.
state: GE
city: Copertino
country: Italy
facility: Ospedale San Giuseppe Da Copertino
state: LE
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Messina
country: Italy
facility: Policlinico G. Martino
state: ME
city: Sesto San Giovanni
country: Italy
facility: Irccs Policlinico Multimedica
state: MI
city: Cuneo
country: Italy
facility: A.O. Santa Croce e Carle
state: Piemonte
city: Roma
country: Italy
facility: Ospedale Sandro Pertini
state: RM
city: Chieri
country: Italy
facility: Ospedale Maggiore
state: TO
city: Torino
country: Italy
facility: Ospedale Mauriziano
state: TO
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria
state: TR
city: Trieste
country: Italy
facility: Aas 1 Triestina
state: TS
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Napoli
country: Italy
facility: Aorn Osp. Dei Colli- Po Vincenzo Monaldi
city: Napoli
country: Italy
facility: Seconda Universita' Di Napoli
city: Trento
country: Italy
facility: Casa di Cura Villa Bianca
Study officials:
affiliation: Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri
name: Carlo B. Giorda, MD
role: STUDY_CHAIR
References:
citation: Giorda CB, Cioffi G, Lucci D, Nada E, Ognibeni F, Mancusi C, Latini R, Maggioni AP; DYDA 2 Investigators. Effects of Dipeptidyl Peptidase-4 Inhibitor Linagliptin on Left Ventricular Dysfunction in Patients with Type 2 Diabetes and Concentric Left Ventricular Geometry (the DYDA 2 Trial). Rationale, Design, and Baseline Characteristics of the Study Population. Cardiovasc Drugs Ther. 2019 Oct;33(5):547-555. doi: 10.1007/s10557-019-06898-6.
citation: Cioffi G, Giorda CB, Lucci D, Nada E, Ognibeni F, Mancusi C, Latini R, Maggioni AP; DYDA 2 investigators. Effects of linagliptin on left ventricular DYsfunction in patients with type 2 DiAbetes and concentric left ventricular geometry: results of the DYDA 2 trial. Eur J Prev Cardiol. 2021 Mar 23;28(1):8-17. doi: 10.1177/2047487320939217. Epub 2020 Jul 28.