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

Diabetes Mellitus, Type 2 Clinical Trial

— DYDA2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02851745
• Other study ID #: G113
• Status: Completed
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: July 2, 2019

Study information

• Verified date: July 2019
• Source: Heart Care Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: July 2, 2019
• Est. primary completion date: July 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Left Ventricular Systolic Dysfunction

Intervention

Drug:
• Linagliptin

• Placebo

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Papa Giovanni Xxiii	Bergamo	BG
Italy	P.O. Garibaldi-Nesima	Catania	CT
Italy	Ospedale Maggiore	Chieri	TO
Italy	Ospedale San Giuseppe Da Copertino	Copertino	LE
Italy	A.O. Santa Croce e Carle	Cuneo	Piemonte
Italy	Ospedale Villa Scassi	Genova	GE
Italy	Policlinico G. Martino	Messina	ME
Italy	Centro Cardiologico Monzino	Milano
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	Aorn Osp. Dei Colli- Po Vincenzo Monaldi	Napoli
Italy	Seconda Universita' Di Napoli	Napoli
Italy	Iclas-Istituto Clinico Ligure Alta Spec.	Rapallo	GE
Italy	Ospedale Sandro Pertini	Roma	RM
Italy	Ospedale Casa Sollievo Della Sofferenza	San Giovanni Rotondo	FG
Italy	Irccs Policlinico Multimedica	Sesto San Giovanni	MI
Italy	Azienda Ospedaliera Santa Maria	Terni	TR
Italy	Ospedale Mauriziano	Torino	TO
Italy	Casa di Cura Villa Bianca	Trento
Italy	Aas 1 Triestina	Trieste	TS

Sponsors (2)

Lead Sponsor	Collaborator
Heart Care Foundation	Fondazione dell'Associazione Medici Diabetologi

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in LV systolic function	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).	48 weeks
Secondary	Changes in diastolic LV function	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.	48 weeks