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

Official 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”

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.

Intervention(s) in this Clinical Trial

• Drug: Aliskiren
  • Aliskiren 300 mg tablets taken orally once daily
• Drug: Amlodipine
  • Amlodipine 5 mg capsule taken orally once daily
• Drug: Placebo Aliskiren
  • Placebo Aliskiren taken orally once daily.
• Drug: Placebo Amlodipine
  • Placebo Amlodipine taken orally once daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Aliskiren 300 mg
  • Eligible 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.
• Active Comparator: Amlodipine 5 mg
  • Eligible 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 Measures

• 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
    Safety Issue?: No

Secondary Measures

• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00417170

Study ID Number: CSPP100A2239

ClinicalTrials.gov Identifier: NCT00417170

Health Authority: United States: Food and Drug Administration