Diastolic Dysfunction in Patients With Type 2 Diabetes Mellitus

Phase 3

Terminated

• Conditions: Diabetes Mellitus Type 2 (T2DM); Left Ventricular Diastolic Dysfunction
• Interventions: Drug: placebo; Drug: Linagliptin

• Registration Number: NCT01888796
• Lead Sponsor: RWTH Aachen University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2013-06-20
• Study First Submitted QC: 2013-06-25
• Study First Posted: 2013-06-28
• Study Start: 2013-09
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2015-02
• Last Update Submitted: 2017-04-10
• Last Update Posted: 2017-04-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo (tablets) once daily for 6 month
Linagliptin	Linagliptin	Linagliptin 5 mg (tablets) once daily for 6 month

Primary Outcome Measures

Name	Time	Method
Change in left ventricular diastolic function	baseline and 6 months	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

Secondary Outcome Measures

Name	Time	Method
Change in serum NT-pro BNP levels	baseline and 6 months	Change in serum NT-pro BNP levels

Trial Locations

Locations (1)

Department of Internal Medicine I, University Hospital; 🇩🇪 Aachen, Germany