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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 2; Left Ventricular Systolic Dysfunction
• Interventions: Drug: Placebo; Drug: Linagliptin

• Registration Number: NCT02851745
• Lead Sponsor: Heart Care Foundation

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.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2016-07-28
• Study First Submitted QC: 2016-08-01
• Study First Posted: 2016-08-02
• Status Verified: 2019-07
• Primary Completion: 2019-07-02
• Study Completion: 2019-07-02
• Last Update Submitted: 2021-05-21
• Last Update Posted: 2021-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 188

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 5 mg daily for 48 weeks
Linagliptin	Linagliptin	Linagliptin 5 mg daily for 48 weeks

Primary Outcome Measures

Name	Time	Method
Increase in LV systolic function	48 weeks	Statistically significant change (equivalent to an increase of 10%) from baseline to 48 weeks of LV systolic function measured by analysis of the MFS (centralized reading).

Secondary Outcome Measures

Name	Time	Method
Changes in diastolic LV function	48 weeks	* Changes from baseline to 48 weeks of diastolic LV function (centralized reading) classified, in the two moments of evaluation, in 4 stages: normal, mild dysfunction, moderate and severe dysfunction. The efficacy of treatment will be evaluated both in terms of significant reduction of the parameter E / E 'expressed as a continuous variable and as entity improvement of dysfunction analyzed by degrees, as described above.; * Changes from baseline to 48 weeks of longitudinal LV systolic function (centralized reading) measured by tissue Doppler (peak systolic velocity of the wave S 'mitral ring); percentage of patients showing an improvement of S '\> 25% from baseline.

Trial Locations

Locations (19)

Ospedale Sandro Pertini; 🇮🇹 Roma, RM, Italy

Ospedale Casa Sollievo Della Sofferenza; 🇮🇹 San Giovanni Rotondo, FG, Italy

Iclas-Istituto Clinico Ligure Alta Spec.; 🇮🇹 Rapallo, GE, Italy

Policlinico G. Martino; 🇮🇹 Messina, ME, Italy

Azienda Ospedaliera Papa Giovanni Xxiii; 🇮🇹 Bergamo, BG, Italy

Ospedale Villa Scassi; 🇮🇹 Genova, GE, Italy

Aas 1 Triestina; 🇮🇹 Trieste, TS, Italy

Casa di Cura Villa Bianca; 🇮🇹 Trento, Italy

Centro Cardiologico Monzino; 🇮🇹 Milano, Italy

Irccs Policlinico Multimedica; 🇮🇹 Sesto San Giovanni, MI, Italy

A.O. Santa Croce e Carle; 🇮🇹 Cuneo, Piemonte, Italy

Ospedale Maggiore; 🇮🇹 Chieri, TO, Italy

Ospedale Mauriziano; 🇮🇹 Torino, TO, Italy

Azienda Ospedaliera Santa Maria; 🇮🇹 Terni, TR, Italy

Aorn Osp. Dei Colli- Po Vincenzo Monaldi; 🇮🇹 Napoli, Italy

Seconda Universita' Di Napoli; 🇮🇹 Napoli, Italy

P.O. Garibaldi-Nesima; 🇮🇹 Catania, CT, Italy

Ospedale San Giuseppe Da Copertino; 🇮🇹 Copertino, LE, Italy

Ospedale San Raffaele; 🇮🇹 Milano, Lombardia, Italy