Official Title: “A Double-Blind, Double Dummy, Randomized Parallel Design Trial to Evaluate the Effects of 12 Weeks of Treatment With 300 mg Aliskiren Compared to 5 mg Amlodipine on Insulin Resistance and Coronary Endothelial Function in Hypertensive Patients With Metabolic Syndrome”

This study will evaluate the safety and efficacy of aliskiren and amlodipine on coronary endothelial function in patients with metabolic syndrome and hypertension after 12 weeks of treatment.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: Aliskiren
• Drug: Amlodipine

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Aliskiren
• Active Comparator: 2
  • Amlodipine

Primary Measures

• Effects of aliskiren on coronary endothelial function and insulin sensitivity following 12 weeks of treatment compared to Amlodipine in patients with metabolic syndrome and mild to moderate hypertension.

Secondary Measures

• Effect of Aliskiren on peripheral arterial compliance/ vascular stiffness by Pulse Wave Analysis (PWA) compared to Amlodipine.
• Relationship between the effects of Aliskiren on insulin resistance and endothelial dysfunction, biomarkers of vascular inflammation (including adipocytokines) and other markers of vascular and/or metabolic disease.

Inclusion Criteria:

• Male or female adults aged 18 to 55 years and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Sitting blood pressure ≥ 130/80 mmHg at 2 consecutive study visits (Visits 1 and 2).
• Metabolic Syndrome as defined by the ATP III criteria. Subjects should have hypertension (defined above) and IGT plus one or more out of the remaining 3 criteria to satisfy entry into the study. Patients must be IGT positive but may be negative or positive for IFG. IGT will be classified according to ADA guidelines (Fasting Glucose: 100mg/dL to 125mg/dL and 2 Hour Glucose: 140mg/dL to 199mg/dL).
• Abnormal PET results at baseline. Abnormal PET results will be defined by MBFCPT of less than or equal to 35%.
• Abnormal euglycemic clamp results at baseline. Abnormal euglycemic clamps will be defined as GINF of less than or equal to 4.2 mg/kg/min.
• BMI of less than 40.

Exclusion Criteria:

• Smokers (use of tobacco products in the recent past). Smokers will be defined as any subject who reports cigarette use or has a urine cotinine greater than 200 ng/mL.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study.
• Recent history of cardiovascular abnormalities.; a medical history of clinically significant ECG abnormalities, including history of a prolonged QT-interval syndrome.
• Blood pressure ≥ 160 mmHg systolic or ≥110 mmHg diastolic after lying down for at least 3 minutes in supine position
• History of significant autonomic dysfunction (for example, fainting) .
• History or presence of severe lung disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
• History of clinically significant drug allergy, atopic allergy (asthma, urticaria, eczematous dermatitis). And known sensitivity to amlodipine or the investigational drug.
• Taking antihypertensive, lipid-lowering, oral antidiabetic drugs or any medication that alters insulin sensitivity, the renin-angiotensin system, lipids or endothelial function within the past 6 months.
• 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: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Novartis

Overall Clinical Trial Officials and Contacts

Novartis Principal Investigator Investigator site  

Overall Contact: Novartis EH 862-778-8300 

Information obtained from ClinicalTrials.gov on August 28, 2008

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