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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Peter Rossing, Steno Diabetes Center
ClinicalTrials.gov Identifier:
NCT01499108
First received: December 12, 2011
Last updated: November 27, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes
Drug: liraglutide
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Time Course of the Blood Pressure Lowering Effect of Liraglutide Therapy in Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Steno Diabetes Center:

Primary Outcome Measures:
  • Change in ambulatory blood pressure [ Time Frame: 50 days ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Change in ECV [ Time Frame: 50 days ] [ Designated as safety issue: No ]
    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).

  • Washout analysis [ Time Frame: 21 ] [ Designated as safety issue: No ]
    Change in 24h BP, ECV, weight, arterial stiffness from day 49 to day 70th


Estimated Enrollment: 35
Study Start Date: August 2012
Estimated Study Completion Date: August 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liraglutide
single-group study were participants recieve Liraglutide
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
Other Name: Victoza

Detailed 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499108

Locations
Denmark
Steno Diabetes Center
Gentofte, Denmark, 2820
Sponsors and Collaborators
Peter Rossing
Novo Nordisk A/S
Investigators
Principal Investigator: Peter Rossing, MD Steno Diabetes Centes
  More Information

No publications provided

Responsible Party: Peter Rossing, Director of Research, Chief Physician, DMSc, Steno Diabetes Center
ClinicalTrials.gov Identifier: NCT01499108     History of Changes
Other Study ID Numbers: 2011-005344-95
Study First Received: December 12, 2011
Last Updated: November 27, 2013
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Steno Diabetes Center:
type 2 diabetes
hypertension
liraglutide
kidney function

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014