Clinical trial NCT00417170: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High Blood Pressure
Metabolic Syndrome
Insulin Resistance
Endothelial Dysfunction
Keywords: High Blood pressure
Hypertension
metabolic syndrome
insulin resistance
endothelial dysfunction
pre-diabetic
amlodipine,
aliskiren,
IGT,
IFG,
MBF
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-29
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment
timeFrame: At baseline and after 12 weeks of treatment
Secondary outcomes:
measure: Mean Change in Insulin Sensitivity as Measured by Glucose Infusion Rate (Last 30 Minutes) From Baseline and After 12 Weeks of Treatment.
timeFrame: At baseline and after 12 weeks of treatment
measure: Mean Change in Insulin Concentration as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment
timeFrame: At baseline and after 12 weeks of treatment
measure: 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
timeFrame: Baseline and after 12 weeks of treatment
measure: Mean Change in Arterial Compliance as Measured by Pulse Wave Analysis From Baseline and After 12 Weeks of Treatment
timeFrame: At baseline and after 12 weeks of treatment
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: