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Comparison of Aliskiren and Amlodipine on Insulin Resistance and Endothelial Dysfunction in Patients With Hypertension and Metabolic Syndrome

Phase 2
Completed
Conditions
High Blood Pressure
Metabolic Syndrome
Insulin Resistance
Endothelial Dysfunction
Interventions
Registration Number
NCT00417170
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

The purpose of this study was to determine the effects of Aliskiren on insulin resistance (IR) and endothelial dysfunction (ED) in patients with high blood pressure and metabolic syndrome. The efficacy of Aliskiren was compared to Amlodipine.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Amlodipine 5 mgPlacebo AliskirenEligible participants received oral Amlodipine 5 mg + Placebo Aliskiren once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.
Aliskiren 300 mgPlacebo AmlodipineEligible participants received oral Aliskiren 300 mg + Placebo Amlodipine once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.
Aliskiren 300 mgAliskirenEligible participants received oral Aliskiren 300 mg + Placebo Amlodipine once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.
Amlodipine 5 mgAmlodipineEligible participants received oral Amlodipine 5 mg + Placebo Aliskiren once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.
Primary Outcome Measures
NameTimeMethod
Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of TreatmentAt baseline and after 12 weeks of treatment

MBF is measured by Positron Emission Tomography (PET) first at rest, then 45 minutes later, during cold pressor testing (CPT). The patient is placed in the PET scanner and injected with N-13 ammonia as a tracer. PET images are taken to assess myocardial blood flow at rest. After 40 minutes, the patient immerses one hand in ice water and PET images are taken to assess myocardial blood flow at sympathetic activation. Change from baseline data is analyzed by an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.

Secondary Outcome Measures
NameTimeMethod
Mean Change in Insulin Concentration as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of TreatmentAt baseline and after 12 weeks of treatment

Insulin Concentration is determined by the Oral Glucose Tolerance Test (OGTT) which begins after a 10 hour overnight fast. Blood samples are taken at baseline and after an oral 75 gram dose of glucose. Additional samples of blood are taken to measure glucose and insulin levels at 30, 60, 120 and 180 minutes post glucose intake. Changes from pre-glucose intake values are analyzed by an analysis of variance (ANOVA) model including treatment, visit and post-dose time points ( 30, 60, 120 and 180 minutes) as fixed factors and subject (nested in treatment) as a random factor.

Mean Change From Baseline in Inflammatory Marker ( C-peptide) as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment [Time Frame: At Baseline and After 12 Weeks of TreatmentBaseline and after 12 weeks of treatment

C-peptide level is determined by the Oral Glucose Tolerance Test (OGTT) which begins after a 10 hour overnight fast. Blood samples are taken at baseline and after an oral 75 gram dose of glucose. Additional samples of blood are taken to measure glucose and insulin levels at 30, 60, 120 and 180 minutes post glucose intake. Changes from pre-glucose intake values are analyzed by an analysis of variance (ANOVA) model including treatment, visit and post-dose time points ( 30, 60, 120 and 180 minutes) as fixed factors and subject (nested in treatment) as a random factor.

Mean Change in Insulin Sensitivity as Measured by Glucose Infusion Rate (Last 30 Minutes) From Baseline and After 12 Weeks of Treatment.At baseline and after 12 weeks of treatment

Insulin sensitivity is measured by the hyperglycemic euglycemic clamp procedure where a supine patient has 2 IV lines inserted for sampling blood. Regular human insulin (60mU/m\^2 surface area/min) is infused for 120 minutes. Dextrose (20% w/v) is infused to maintain glycemia at \< 100 mg/dL and is adjusted based on plasma glucose levels obtained every 5 minutes. Blood for glucose and insulin is taken at specified time intervals. Change from baseline data is analyzed by analysis of variance model including treatment and week as fixed factors, and subject (nested in treatment) as a random factor.

Mean Change in Arterial Compliance as Measured by Pulse Wave Analysis From Baseline and After 12 Weeks of TreatmentAt baseline and after 12 weeks of treatment

Arterial Compliance is determined by Pulse Wave Analysis measured by a detector placed at the carotid artery while taking ECG and tonometry at the same time. Procedure is repeated for the femoral artery. Pulse Wave data are calculated by dividing distance between 2 arteries by the difference between the rise delay of the distal pulse wave and the R wave of the QRS complex and the rise delay of the proximal pulse wave to the QRS complex. Data analysis used an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.

Trial Locations

Locations (1)

Novartis Investigative Site

🇺🇸

Santa Monica, California, United States

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