Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— Liratime  

Official title:

Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01499108
• Other study ID #: 2011-005344-95
• Status: Completed
• Phase: Phase 4
• First received: December 12, 2011
• Last updated: January 30, 2015
• Start date: August 2012
• Est. completion date: August 2014

Study information

• Verified date: July 2013
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Background: Preclinical blood pressure (BP) data from studies of hypoglycemic effects of liraglutide treatment (the LEAD program), revealed a significant antihypertensive potential. The time course and the mechanism behind this effect are unknown.

Objectives: To evaluate the time course of the antihypertensive effect of liraglutide treatment in patients with type 2 diabetes

Design: Open-label study with intervention and subsequent washout period

Patient Population: 35 hypertensive (SBP ≥130 mm Hg and DBP ≥80 mmHg) patients with type 2 diabetes.

Intervention: All patients will be treated with liraglutide 0.6 mg once daily for 7 days and will then be titrated to 1.2 mg once daily for 14 days and then titrated to 1.8 mg once daily for 4 weeks. This is followed by a washout period of 3 weeks without liraglutide treatment.

Endpoints: 24-hour blood pressure, natriuresis, extra cellular volume (ECV

Description:

Hypotheses Primary hypothesis • Liraglutide treatment causes a reduction in 24h BP

Secondary hypothesis:

• The effect on BP may be mediated by an increase in natriuresis, thereby affecting ECV

• The effect on BP may be mediated by a decrease in arterial stiffness and central aortic pressure

Purpose Primary purpose

• To assess how quickly the antihypertensive effect of liraglutide treatment set in after initiation in patients with type 2 diabetes

Secondary objectives

• To measure the effect of liraglutide treatment on natriuresis.

• To measure the effect of liraglutide treatment on ECV

• To measure the effect of liraglutide treatment on arterial stiffness

• To measure weight change after initiation of liraglutide treatment

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must give written informed consent before participation. Patient information and consent form must be approved by the Danish Medicines Agency and the Regional Scientific Ethical Committee

2. Male or female patients > 18 years with type 2 diabetes (WHO criteria).

3. Patients must be on treatment with metformin. Any form of treatment with SU compounds will be discontinued and washed out for two weeks prior to the start of study drug.

4. eGFR = 60 ml/min/1.73 m2 (estimated by MDRD formula)

5. Fertile female patients must use chemical, hormonal and mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening

6. Patients must be on antihypertensive treatment or having elevated blood pressure (SBP =130 mm Hg and DBP =80 mmHg), lower than 170/105 mm Hg at baseline and the patients must be stable antihypertensive medication for at least 4 weeks prior to baseline

7. Patients must be on stable hypoglycemic medication for at least two weeks before the first visit.

8. Must be able to communicate with the investigator

Exclusion Criteria:

1. Ongoing insulin therapy

2. BP > 170/105 mm Hg at baseline

3. Type 1 diabetes mellitus

4. Chronic pancreatitis / previous acute pancreatitis

5. Known or suspected hypersensitivity to trial product(s) or related products.

6. Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening

7. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial

8. Inflammatory bowel disease

9. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months

10. Previous bowel resection

11. Body mass index <18.5 kg/m2

12. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods

13. Clinical signs of diabetic gastroparesis

14. Impaired liver function (transaminases > two times upper reference levels)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• liraglutide
Subcutaneous injection of liraglutide at doses of 0.6, 1.2, and 1.8 mg once daily during the 49 days duration of the study

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte

Sponsors (2)

Lead Sponsor	Collaborator
Peter Rossing	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ambulatory blood pressure	Change in 24h BP from day 1 to day 49 (baseline to end of treatment) and time to statistically significant change in BP 24h after initiation of or increased dose of liraglutide	50 days	No
Secondary	Change in ECV	Changes in ECV (measured by GFR), urinary sodium, weight, arterial stiffness and daily home-BP, from day 1 to day 49 (baseline to end of treatment).	50 days	No
Secondary	Washout analysis	Change in 24h BP, ECV, weight, arterial stiffness from day 49 to day 70th	21	No