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

NCT00417170 | Completed Phase 2 Results

• 1 other identifier: CSPP100A2239
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From 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.

  At baseline and after 12 weeks of treatment

Secondary Outcomes (4)

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

  At baseline and after 12 weeks of treatment

• Mean Change in Insulin Concentration as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment

  At baseline and after 12 weeks of treatment

• 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

  Baseline and after 12 weeks of treatment

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

  At baseline and after 12 weeks of treatment

Study Arms (2)

Aliskiren 300 mg

EXPERIMENTAL

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.

Drug: Aliskiren; Drug: Placebo Amlodipine

Amlodipine 5 mg

ACTIVE COMPARATOR

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.

Drug: Amlodipine; Drug: Placebo Aliskiren

Interventions

Aliskiren DRUG

Aliskiren 300 mg tablets taken orally once daily

Aliskiren 300 mg

Amlodipine DRUG

Amlodipine 5 mg capsule taken orally once daily

Amlodipine 5 mg

Placebo Aliskiren DRUG

Placebo Aliskiren taken orally once daily.

Amlodipine 5 mg

Placebo Amlodipine DRUG

Placebo Amlodipine taken orally once daily

Aliskiren 300 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Hypertension; Metabolic Syndrome; Insulin Resistance; Glucose Intolerance

Interventions

aliskiren; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2006
• First Posted: December 29, 2006
• Study Start: October 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: September 26, 2011
• Results First Posted: August 11, 2011

Record last verified: 2011-09

Locations

US (1)