The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus - Full Text View

Sponsor:	Novo Nordisk
Information provided by:	Novo Nordisk
ClinicalTrials.gov Identifier:	NCT00620282

Purpose

This trial is conducted in the United States of America (USA). The purpose of the trial is to assess the effect of liraglutide on forearm blood flow in subjects with type 2 diabetes who are on diet and lifestyle changes or treated with metformin alone.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: liraglutide Drug: placebo Drug: glimepiride	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride Arm

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Glimepiride Liraglutide

U.S. FDA Resources

Further study details as provided by Novo Nordisk:

Primary Outcome Measures:

Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Assessed endothelial function by measuring the change in ACh-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.

Secondary Outcome Measures:

Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Assessed endothelial function by measuring the change in SNP-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.
Change in HbA1c (Glycosylated Haemoglobin A1c) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Percentage point change in HbA1c
Change in Fasting Plasma Glucose (FPG) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in FPG
Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
The 7-point profile included plasma glucose measurements at the following time points: before each main meal (breakfast, lunch and dinner), 90 minutes after the start of each main meal (breakfast, lunch and dinner) and at bedtime.
Change in Body Weight [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Fasting Lipid Profile - Change in Total Cholesterol (TC) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in TC
Fasting Lipid Profile - Change in LDL-C [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in LDL-C
Fasting Lipid Profile - Change in HDL-C [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in HDL-C
Fasting Lipid Profile - Change in Triglycerides (TG) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in TG
Biomarkers of Cardiovascular Risk - Change in TNF-alpha [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
Change in TNF-alpha
Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range [ Time Frame: week 0, week 12 ] [ Designated as safety issue: Yes ]
Number of subjects with serum BUN values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 6.000 mg/dL, upper value 21.000 mg/dL) Male (lower value 8.000 mg/dL, upper value 25.000 mg/dL).
Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range [ Time Frame: week 0, week 12 ] [ Designated as safety issue: Yes ]
Number of subjects with serum creatinine values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 0.600 mg/dL, upper value 1.100 mg/dL) Male (lower value 0.800 mg/dL, upper value 1.300 mg/dL).
Number of Hypoglycaemic Episodes [ Time Frame: weeks 0-12 ] [ Designated as safety issue: Yes ]
Total number of hypoglycaemic episodes occurring from week 0 to week 12. Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself and either plasma glucose was below 56 mg/dL or symptoms were reversed after food intake or glucagon/intravenous glucose administration. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

Enrollment:	49
Study Start Date:	February 2008
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lira 1.8 Liraglutide 1.8 mg administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)	Drug: liraglutide Stepwise dose increase, s.c. (under the skin) injection, once daily
Placebo Comparator: Placebo Placebo administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)	Drug: placebo Liraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily
Active Comparator: Glimepiride Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12	Drug: glimepiride Tablets, 1 - 4 mg daily

Eligibility

Ages Eligible for Study:	40 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetes
Diet and lifestyle changes or metformin monotherapy for at least three months
HbA1c (glycosylated haemoglobin) 6.5-9.0% (both inclusive)
Body Mass Index (BMI) less than or equal to 40 kg/m^2

Exclusion Criteria:

Previous treatment with insulin (except for short term treatment with insulin in connection with intercurrent illness, at the discretion of the Investigator)
Previous treatment with glucagon-like peptide-1 (GLP-1) analogues/mimetics, including treatment in a clinical trial
Treatment with any oral hypoglycaemic agents other than metformin in a period of 3 months prior to screening
Current smoker or history of smoking within 6 months prior to screening
Evidence of overt cardiovascular disease (documented coronary heart disease, class II-IV congestive heart failure, cerebrovascular disease, or peripheral vascular disease)
Abnormal, clinically significant exercise stress electrocardiogram (ECG) test, as judged by the Investigator
Known retinopathy or maculopathy requiring acute treatment, as judged by the Investigator
Known autonomic neuropathy, as judged by the Investigator
Initiation or change (dose or treatment regimen) in concomitant blood pressure-lowering or lipid-lowering medication within 4 weeks prior to screening
Systolic blood pressure more than or equal to 140 mmHg and/or diastolic blood pressure more than or equal to 90 mmHg

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620282

Locations

United States, Minnesota
Novo Nordisk Clinical Trial Call Center
Rochester, Minnesota, United States, 55905-0001

Sponsors and Collaborators

Novo Nordisk

Investigators

Study Director:

Jason Brett, MD

Novo Nordisk

More Information

Additional Information:

Clinical Trials at Novo Nordisk This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier:	NCT00620282 History of Changes
Other Study ID Numbers:	NN2211-1799
Study First Received:	February 11, 2008
Results First Received:	May 19, 2011
Last Updated:	June 16, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs

Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on February 09, 2012