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NCT Number: NCT00417170

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

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.

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Key information

Conditions

High Blood Pressure Cardiovascular Diseases Endothelial Dysfunction Glucose Intolerance Glucose Metabolism Disorders Hyperglycemia Hyperinsulinism Hypertension Insulin Resistance Metabolic Diseases Metabolic Syndrome Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site

Santa Monica, California, 90404, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female adults aged 18 to 55 years, inclusive.
  • Sitting diastolic blood pressure ≥80 mm Hg and/or sitting systolic blood pressure ≥ 130 at screening.
  • Metabolic Syndrome as defined by the Adult Treatment Panel (ATP) III criteria.
  • Hypertension (defined above) and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) plus one or more out of the remaining 3 criteria to satisfy entry into the study. IGT and IFG will be classified according to American Diabetes Association (ADA) guidelines:
  • IFG: Fasting plasma glucose of 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)
  • IGT: Two-hour plasma glucose of 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)
  • Abnormal Positron Emission Tomography (PET) results at baseline. (Myocardial Blood Flow (MBF) of less than or equal to 35%.)
  • Abnormal euglycemic clamp results at baseline. (Glucose infusion rate (GINF) of less than or equal to 4.2 mg/kg/min.)
  • Body mass index (BMI) of less than 40.

Exclusion criteria

  • Smokers (use of tobacco products in the recent past)
  • Cardiovascular abnormalities including myocardial infarction, angina pectoris, hypertensive encephalopathy, stroke, transient ischemic attack, valvular heart disease, ventricular arrhythmia, A-V block, atrial fibrillation or cardiac revascularization/angioplasty in the past 12 months.
  • Symptoms or clinical evidence of congestive heart failure or known left ventricular ejection fraction < 40%.
  • Supine Blood pressure ≥ 160 mmHg systolic or ≥110 mmHg diastolic.
  • Clinically significant echocardiogram (ECG) abnormalities, including history of a prolonged QT-interval syndrome.
  • Significant autonomic dysfunction.
  • Severe bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
  • Clinically significant drug allergy, atopic allergy (asthma, urticaria, eczematous dermatitis).
  • Pregnant or breastfeeding females. Pre-menopausal females who are not practicing a non-hormonal method of birth control.
  • African Americans will not be eligible for this study.

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

Aliskiren

Drug

Aliskiren 300 mg tablets taken orally once daily

Amlodipine

Drug

Amlodipine 5 mg capsule taken orally once daily

Placebo Aliskiren

Drug

Placebo Aliskiren taken orally once daily.

Placebo Amlodipine

Drug

Placebo Amlodipine taken orally once daily

Primary outcomes

  1. Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment

    Time frame: At 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 outcomes

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

    Time frame: 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.

  2. Mean Change in Insulin Concentration 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 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.

  3. 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 Treatment

    Time frame: Baseline 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.

  4. Mean Change in Arterial Compliance as Measured by Pulse Wave Analysis From Baseline and After 12 Weeks of Treatment

    Time frame: At 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Double-blind, Double Dummy, Randomized Parallel Design Trial to Study the Effects of 12 Weeks of Treatment With 300mg Aliskiren vs. 5mg Amlodipine on Insulin Resistance and Endothelial Dysfunction in Hypertensive Patients With Metabolic Syndrome

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Dec 29, 2006
Registry last updated
Sep 26, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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