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

Novartis

Status and phase: Completed; Phase 2

Conditions: High Blood Pressure; Endothelial Dysfunction; Insulin Resistance; Metabolic Syndrome

Treatments: Drug: Placebo Aliskiren; Drug: Aliskiren; Drug: Amlodipine; Drug: Placebo Amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00417170

CSPP100A2239

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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48 participants in 2 patient groups

Aliskiren 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Aliskiren

Drug: Placebo Amlodipine

Amlodipine 5 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo Aliskiren

Drug: Amlodipine