Working… Menu

Assessment of Renin Inhibition on Insulin Sensitivity, Diastolic Function and Aortic Compliance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01252238
Recruitment Status : Terminated (Study sponsor terminated study due to AE's reported with valsartan and aliskiren)
First Posted : December 2, 2010
Results First Posted : September 5, 2013
Last Update Posted : February 13, 2018
Information provided by (Responsible Party):
Jonathan S. Williams, MD, MMSc, Brigham and Women's Hospital

Brief Summary:

This study is an investigation of the effect of commonly prescribed anti-hypertensive agents on insulin sensitivity, diastolic function and aortic compliance. The aims of the study are as follows:

Specific Aim 1: To determine in insulin resistant, hypertensive subjects if renin inhibition for 12 weeks modifies glucose homeostasis and insulin sensitivity.

To accomplish this specific aim, we will use three approaches: a fasting HOMA Index; and a three hour glucose tolerance test. Only hypertensive subjects with insulin resistance, as assessed by HOMA index will be enrolled in the study. Insulin resistance will be assessed basally and after twelve weeks of treatment with either a calcium channel blocker with placebo, or calcium channel blocker with a renin inhibitor, or a calcium channel blocker with a renin inhibitor and an angiotensin receptor antagonist.

Specific Aim 2: To determine in insulin resistant, hypertensive subjects if renin inhibition for 12 weeks modifies diastolic function and aortic compliance response to dietary sodium intake.

The same protocol and subjects will be used as defined in Specific Aim 1. Myocardial relaxation velocity (tissue Doppler imaging at the mitral annulus) and aortic compliance (characteristic aortic impedance) will be measured at baseline and then after acute and chronic renin inhibition:

  1. Acute effect of renin inhibition: Hemodynamic measurements will be obtained on both high and low dietary sodium intake conditions (~1 week each) before and after a single dose of a renin inhibitor.
  2. Chronic effect of renin inhibition: Hemodynamic measurements will be obtained at baseline and after 12 weeks of each of the three drug treatment arms above.

The study lasts 12 weeks and plans to study 45 hypertensive adults over the next two years.

Condition or disease Intervention/treatment Phase
Insulin Sensitivity Aortic Compliance Diastolic Function Drug: Aliskiren Drug: Valsartan and Aliskiren Drug: Amlodipine Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Renin Inhibition on Insulin Sensitivity, Diastolic Function and Aortic Compliance
Study Start Date : June 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
Placebo Comparator: Valsartan and Aliskiren
Valsartan 150 mg and Aliskiren (150 mg followed by force titration to 300 mg)
Drug: Valsartan and Aliskiren
Subject taking combination of valsartan and aliskiren.

Experimental: Aliskiren Drug: Aliskiren
Aliskiren 150 mg daily for 10 weeks, force titrated after initial 2 weeks.

Placebo Comparator: Placebo Group
Only taking Amlodipine
Drug: Amlodipine
Taking Amlodipine as prescribed by MD for management of high blood pressure.

Primary Outcome Measures :
  1. Change in Insulin Sensitivity by HOMA at 12 Weeks [ Time Frame: 12 weeks ]
    The difference (change) in HOMA calculated as Baseline HOMA minus 12-week HOMA value

Secondary Outcome Measures :
  1. Aortic Compliance [ Time Frame: 12 weeks ]
    Characteristic aortic imedeance, dynes x s/cm5

Other Outcome Measures:
  1. Pulse Wave Velocity [ Time Frame: 12 weeks ]
    Measure of pulsewave velocity cm/s

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men and women, 18-70 years old
  • BMI =/< 35
  • BP: BP > 145/95 on no BP medication or on 3 or less BP medications
  • HOMA =>2.5
  • Any race

Exclusion Criteria:

  • 4 or more BP medications
  • Intolerance or known prior adverse history from taking the medications amlodipine, aliskiren or valsartan
  • BP >170/110 on screening exam
  • Alcohol intake >12 oz per week
  • Current smoking
  • Recreational drug use
  • Known or suspected secondary hypertension
  • Known history of coronary artery disease, cerebrovascular disease or congestive heart failure
  • History or known kidney disease (eGFR <50cc/min)
  • Diabetes or current metformin use, or HbA1c >=6.5% on screen
  • Steroid use (oral or inhaled, chronic or within the past 6 months)
  • Clinically significant screening lab abnormalities (See attached "Screening Labs Acceptable Ranges")
  • Evidence of ischemia or heart block on screening electrocardiogram (greater than type I-second degree heart block, left bundle branch block, or ST-T wave changes in 2 or more contiguous leads).
  • Acute hospitalizations including surgery in the past 6 months
  • Chronic use of non-steroidal anti-inflammatory or narcotic medications
  • Women who are pregnant or nursing, or wish to become pregnant and/or who can not agree or tolerate two forms of birth control during the study period:

Acceptable birth control methods for use in this study are:

  • hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants
  • barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm)
  • intrauterine device (IUD)
  • abstinence (no sex)
  • Significant concomitant medical illnesses (cancer, chronic active immunological conditions, etc.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01252238

Layout table for location information
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Layout table for investigator information
Principal Investigator: Jonathan Williams, MD Brigham and Women's Hospital

Layout table for additonal information
Responsible Party: Jonathan S. Williams, MD, MMSc, Jonathan Williams, MD, Brigham and Women's Hospital Identifier: NCT01252238     History of Changes
Other Study ID Numbers: 2010p001286
First Posted: December 2, 2010    Key Record Dates
Results First Posted: September 5, 2013
Last Update Posted: February 13, 2018
Last Verified: January 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Insulin Resistance
Immune System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists