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

Primary Purpose

Diabetes Mellitus, Type 2, Left Ventricular Systolic Dysfunction

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Linagliptin
Placebo
Sponsored by
Heart Care Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Azienda Ospedaliera Papa Giovanni Xxiii
  • P.O. Garibaldi-Nesima
  • Ospedale Casa Sollievo Della Sofferenza
  • Ospedale Villa Scassi
  • Iclas-Istituto Clinico Ligure Alta Spec.
  • Ospedale San Giuseppe Da Copertino
  • Ospedale San Raffaele
  • Policlinico G. Martino
  • Irccs Policlinico Multimedica
  • A.O. Santa Croce e Carle
  • Ospedale Sandro Pertini
  • Ospedale Maggiore
  • Ospedale Mauriziano
  • Azienda Ospedaliera Santa Maria
  • Aas 1 Triestina
  • Centro Cardiologico Monzino
  • Aorn Osp. Dei Colli- Po Vincenzo Monaldi
  • Seconda Universita' Di Napoli
  • Casa di Cura Villa Bianca

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Linagliptin

Placebo

Arm Description

Linagliptin 5 mg daily for 48 weeks

Placebo 5 mg daily for 48 weeks

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
July 28, 2016
Last Updated
May 21, 2021
Sponsor
Heart Care Foundation
Collaborators
Fondazione dell'Associazione Medici Diabetologi
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1. Study Identification

Unique Protocol Identification Number
NCT02851745
Brief Title
Effects of Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2, 2019 (Actual)
Study Completion Date
July 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heart Care Foundation
Collaborators
Fondazione dell'Associazione Medici Diabetologi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Left Ventricular Systolic Dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
188 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Linagliptin
Arm Type
Experimental
Arm Description
Linagliptin 5 mg daily for 48 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 5 mg daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Linagliptin
Other Intervention Name(s)
Trajenta
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Increase in LV systolic function
Description
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).
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Changes in diastolic LV function
Description
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.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlo B. Giorda, MD
Organizational Affiliation
Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri
Official's Role
Study Chair
Facility Information:
Facility Name
Azienda Ospedaliera Papa Giovanni Xxiii
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
P.O. Garibaldi-Nesima
City
Catania
State/Province
CT
ZIP/Postal Code
95122
Country
Italy
Facility Name
Ospedale Casa Sollievo Della Sofferenza
City
San Giovanni Rotondo
State/Province
FG
ZIP/Postal Code
71013
Country
Italy
Facility Name
Ospedale Villa Scassi
City
Genova
State/Province
GE
ZIP/Postal Code
16149
Country
Italy
Facility Name
Iclas-Istituto Clinico Ligure Alta Spec.
City
Rapallo
State/Province
GE
ZIP/Postal Code
16035
Country
Italy
Facility Name
Ospedale San Giuseppe Da Copertino
City
Copertino
State/Province
LE
ZIP/Postal Code
73043
Country
Italy
Facility Name
Ospedale San Raffaele
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20010
Country
Italy
Facility Name
Policlinico G. Martino
City
Messina
State/Province
ME
ZIP/Postal Code
98124
Country
Italy
Facility Name
Irccs Policlinico Multimedica
City
Sesto San Giovanni
State/Province
MI
ZIP/Postal Code
20099
Country
Italy
Facility Name
A.O. Santa Croce e Carle
City
Cuneo
State/Province
Piemonte
ZIP/Postal Code
12100
Country
Italy
Facility Name
Ospedale Sandro Pertini
City
Roma
State/Province
RM
ZIP/Postal Code
00157
Country
Italy
Facility Name
Ospedale Maggiore
City
Chieri
State/Province
TO
ZIP/Postal Code
10023
Country
Italy
Facility Name
Ospedale Mauriziano
City
Torino
State/Province
TO
ZIP/Postal Code
10128
Country
Italy
Facility Name
Azienda Ospedaliera Santa Maria
City
Terni
State/Province
TR
ZIP/Postal Code
05100
Country
Italy
Facility Name
Aas 1 Triestina
City
Trieste
State/Province
TS
ZIP/Postal Code
34148
Country
Italy
Facility Name
Centro Cardiologico Monzino
City
Milano
ZIP/Postal Code
20138
Country
Italy
Facility Name
Aorn Osp. Dei Colli- Po Vincenzo Monaldi
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Seconda Universita' Di Napoli
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Casa di Cura Villa Bianca
City
Trento
ZIP/Postal Code
38100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
31418140
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.
Results Reference
background
PubMed Identifier
33755143
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.
Results Reference
result

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

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