Effects of Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry (DYDA2)

May 21, 2021 updated by: Heart Care Foundation

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

188

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20138
        • Centro Cardiologico Monzino
      • Napoli, Italy, 80131
        • Aorn Osp. Dei Colli- Po Vincenzo Monaldi
      • Napoli, Italy, 80131
        • Seconda Universita' Di Napoli
      • Trento, Italy, 38100
        • Casa di Cura Villa Bianca
    • BG
      • Bergamo, BG, Italy, 24127
        • Azienda Ospedaliera Papa Giovanni XXIII
    • CT
      • Catania, CT, Italy, 95122
        • P.O. Garibaldi-Nesima
    • FG
      • San Giovanni Rotondo, FG, Italy, 71013
        • Ospedale Casa Sollievo della Sofferenza
    • GE
      • Genova, GE, Italy, 16149
        • Ospedale Villa Scassi
      • Rapallo, GE, Italy, 16035
        • Iclas-Istituto Clinico Ligure Alta Spec.
    • LE
      • Copertino, LE, Italy, 73043
        • Ospedale San Giuseppe Da Copertino
    • Lombardia
      • Milano, Lombardia, Italy, 20010
        • Ospedale San Raffaele
    • ME
      • Messina, ME, Italy, 98124
        • Policlinico G. Martino
    • MI
      • Sesto San Giovanni, MI, Italy, 20099
        • IRCCS Policlinico Multimedica
    • Piemonte
      • Cuneo, Piemonte, Italy, 12100
        • A.O. Santa Croce e Carle
    • RM
      • Roma, RM, Italy, 00157
        • Ospedale Sandro Pertini
    • TO
      • Chieri, TO, Italy, 10023
        • Ospedale Maggiore
      • Torino, TO, Italy, 10128
        • Ospedale Mauriziano
    • TR
      • Terni, TR, Italy, 05100
        • Azienda Ospedaliera Santa Maria
    • TS
      • Trieste, TS, Italy, 34148
        • Aas 1 Triestina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linagliptin
Linagliptin 5 mg daily for 48 weeks
Drug: Linagliptin
Other Names:
  • Trajenta
Placebo Comparator: Placebo
Placebo 5 mg daily for 48 weeks
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase in LV systolic function
Time Frame: 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).
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in diastolic LV function
Time Frame: 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.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heart Care Foundation

Collaborators

Fondazione dell'Associazione Medici Diabetologi

Investigators

  • Study Chair: Carlo B. Giorda, MD, Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

July 2, 2019

Study Completion (Actual)

July 2, 2019

Study Registration Dates

First Submitted

July 28, 2016

First Submitted That Met QC Criteria

August 1, 2016

First Posted (Estimate)

August 2, 2016

Study Record Updates

Last Update Posted (Actual)

May 25, 2021

Last Update Submitted That Met QC Criteria

May 21, 2021

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • G113

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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