Diabetes Mellitus, Type 2Phase 3DYDA2NCT02851745
Effects of Linagliptin on Left Ventricular Myocardial DYsfunction in Patients With Type 2 DiAbetes Mellitus and Concentric Left Ventricular Geometry
A Phase 3 study testing Linagliptin in people with Diabetes Mellitus, Type 2 and Left Ventricular Systolic Dysfunction, run by Heart Care Foundation at 19 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2, Left Ventricular Systolic Dysfunction
- What is being tested?
- Linagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 188 participants
- Where
- 19 sitesItaly
- Study dates
- Jul 2015to 2 Jul 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 14Show fewer
- 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
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Italy19 sites
Azienda Ospedaliera Papa Giovanni Xxiii
Bergamo, BG, 24127
P.O. Garibaldi-Nesima
Catania, CT, 95122
Ospedale Maggiore
Chieri, TO, 10023
Ospedale San Giuseppe Da Copertino
Copertino, LE, 73043
A.O. Santa Croce e Carle
Cuneo, Piedmont, 12100
Ospedale Villa Scassi
Genova, GE, 16149
Policlinico G. Martino
Messina, ME, 98124
Ospedale San Raffaele
Milan, Lombardy, 20010
Centro Cardiologico Monzino
Milan, 20138
Aorn Osp. Dei Colli- Po Vincenzo Monaldi
Naples, 80131
Seconda Universita' Di Napoli
Naples, 80131
Iclas-Istituto Clinico Ligure Alta Spec.
Rapallo, GE, 16035
Ospedale Sandro Pertini
Roma, RM, 00157
Ospedale Casa Sollievo Della Sofferenza
San Giovanni Rotondo, FG, 71013
Irccs Policlinico Multimedica
Sesto San Giovanni, MI, 20099
Azienda Ospedaliera Santa Maria
Terni, TR, 05100
Ospedale Mauriziano
Torino, TO, 10128
Casa di Cura Villa Bianca
Trento, 38100
Aas 1 Triestina
Trieste, TS, 34148
About this study
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
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.
Read the 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.
- Being tested
- Linagliptin, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinagliptinDrug
Also called Trajenta
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Linagliptin | Experimental | Linagliptin 5 mg daily for 48 weeks Receives: Drug: Linagliptin |
| Placebo | Placebo comparator | Placebo 5 mg daily for 48 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 48 weeks
Secondary outcomes (1)
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2016 (estimated)
- Study startJul 2015
- Primary completion2 Jul 2019
- Study completion2 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heart Care Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione dell'Associazione Medici Diabetologi
- Responsible party
- Sponsor
- Investigators
- Carlo B. Giorda, MD, Study chair, Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02851745
- Sponsor's protocol ID
- G113
- Acronym
- DYDA2
- Status last verified
- Jul 2019
- First submitted
- 28 Jul 2016
- Last updated
- 25 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31418140Cioffi 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.
PubMed 33755143
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02851745
- Acronym / sponsor ID
- DYDA2 / G113
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 188 participants (actual)
- Lead sponsor
- Heart Care FoundationUniversity, hospital or other
- Collaborators
- Fondazione dell'Associazione Medici Diabetologi
- Study start
- Jul 2015
- Primary completion
- 2 Jul 2019 (actual)
- Study completion
- 2 Jul 2019 (actual)
- First posted
- 2 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linagliptin | Experimental | Drug: LinagliptinLinagliptin 5 mg daily for 48 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 5 mg daily for 48 weeks |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LinagliptinAlso: Trajenta | Drug | Linagliptin |
| Placebo | Drug | Placebo |
Primary outcome
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).
1 secondary outcome
Changes in diastolic LV function
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Background: PubMed 31418140Giorda 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 publication: PubMed 33755143Cioffi 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.
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlo B. Giorda, MD study chair
Ospedale Maggiore - Diabetologia Malattie Metaboliche - Chieri
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Linagliptin in people with Diabetes Mellitus, Type 2 and Left Ventricular Systolic Dysfunction, run by Heart Care Foundation at 19 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase in LV systolic function (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02851745, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.