Diastolic Dysfunction in Patients With Type 2 Diabetes Mellitus (Diast Dysfkt)

Effect of Linagliptin Therapy on Myocardial Diastolic Function in Patients With Type 2 Diabetes Mellitus

Examination of the effect of Linagliptin versus placebo on diastolic function in patients with type 2 diabetes mellitus and diastolic dysfunction as assessed by transthoracic echocardiography.

Furthermore the effect on serum levels of NT-pro BNP as a biomarker of heart failure will be investigated.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus Type 2 (T2DM); Left Ventricular Diastolic Dysfunction
• Intervention / Treatment: Drug: Linagliptin; Drug: placebo

Detailed Description

Treatment:

The Patients will receive Linagliptin 5 mg QD or placebo for a period of 6 months.

The echocardiography and 24h RR measurement will be performed at baseline and 6 months after initiation of the therapy.

The blood chemistry (Glucose, HbA1c, BNP) will be evaluated at baseline as well as 3 and 6 months after initiation of the therapy.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Department of Internal Medicine I, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diabetes mellitus Type 2
2. Age > 50 years
3. HbA1c > 7%
4. Left ventricular diastolic dysfunction determined by echocardiography as average E/é ≥13 or average E/é≥8 and LA volume ≥34ml/m2
5. Stable anti-diabetic medication for the last 6 weeks which should include a maximal tolerated dose of metformin (unless contraindication or intolerance to metformin does exist).
6. Indication to increase anti-diabetic medication as judged by the investigator
7. Written informed consent prior to study participation

Exclusion Criteria:

1. Diabetes mellitus type 1

2. Echocardiography:

   • decreased left ventricular systolic function, ejection fraction (EF) <45%
   • regional wall motion abnormalities
   • hypertrophic cardiomyopathy (septum >15mm)
   • severe valvular dysfunction
3. Uncontrolled hypertension
4. Atrial fibrillation
5. Obstructive sleep apnea syndrome
6. Use of DPP-4 Inhibitor (Dipeptidyl-peptidase IV Inhibitor), GLP 1 agonists, Thiazolindinedione
7. Kidney disease CKD 4 and more (GFR < 30 ml/min/1.73)
8. Liver disease (ALT or AST > 3 times the upper limit of norm) or known liver cirrhosis
9. Active malignant disease
10. HbA1c > 8.5%
11. Recent (<3 months) clinically significant coronary or cerebral vascular event
12. Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol.
13. Lactating females
14. The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
15. The subject received an investigational drug within 30 days prior to inclusion into this study
16. The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study
17. The subject is unwilling or unable to follow the procedures outlined in the protocol
18. The subject is mentally or legally incapacitated

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Linagliptin; Linagliptin 5 mg (tablets) once daily for 6 month	Drug: Linagliptin; Other Names: Trade name Trajenta® by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany
Placebo Comparator: Placebo; Placebo (tablets) once daily for 6 month	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular diastolic function	Change in left ventricular diastolic function between baseline and after 6 month as determined by 2D and novel 3D parameter global Strain Rate E Change in left ventricular diastolic function between baseline and after 6 month as determined by standardized parameter E/é and left atrial (LA) volume	baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum NT-pro BNP levels	Change in serum NT-pro BNP levels	baseline and 6 months

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Investigators: Principal Investigator: Nikolaus Marx, Univ.-Prof., Department of Internal Medicine I, RWTH Aachen University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 20, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (Estimate): June 28, 2013

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: T2DM; diastolic dysfunction
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: 12-025; 2012-003858-81 (EudraCT Number); EK 113/13 (Other Identifier: Ethics Committee University Hospital Aachen)