Effects of Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry

NCT ID: NCT02851745

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2019-07-02

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.

Conditions

Diabetes Mellitus, Type 2; Left Ventricular Systolic Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Linagliptin

Linagliptin 5 mg daily for 48 weeks

Group Type: EXPERIMENTAL

Linagliptin

Intervention Type: DRUG

Placebo

Placebo 5 mg daily for 48 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Linagliptin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Trajenta

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione dell'Associazione Medici Diabetologi

UNKNOWN

Sponsor Role: collaborator

Heart Care Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlo B. Giorda, MD

Role: STUDY_CHAIR

Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri

Locations

Azienda Ospedaliera Papa Giovanni Xxiii

Bergamo, BG, Italy

P.O. Garibaldi-Nesima

Catania, CT, Italy

Ospedale Casa Sollievo Della Sofferenza

San Giovanni Rotondo, FG, Italy

Ospedale Villa Scassi

Genova, GE, Italy

Iclas-Istituto Clinico Ligure Alta Spec.

Rapallo, GE, Italy

Ospedale San Giuseppe Da Copertino

Copertino, LE, Italy

Ospedale San Raffaele

Milan, Lombardy, Italy

Policlinico G. Martino

Messina, ME, Italy

Irccs Policlinico Multimedica

Sesto San Giovanni, MI, Italy

A.O. Santa Croce e Carle

Cuneo, Piedmont, Italy

Ospedale Sandro Pertini

Roma, RM, Italy

Ospedale Maggiore

Chieri, TO, Italy

Ospedale Mauriziano

Torino, TO, Italy

Azienda Ospedaliera Santa Maria

Terni, TR, Italy

Aas 1 Triestina

Trieste, TS, Italy

Centro Cardiologico Monzino

Milan, , Italy

Aorn Osp. Dei Colli- Po Vincenzo Monaldi

Napoli, , Italy

Seconda Universita' Di Napoli

Napoli, , Italy

Casa di Cura Villa Bianca

Trento, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 31418140 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33755143 (View on PubMed)

Other Identifiers

G113

Identifier Type: -

Identifier Source: org_study_id