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

This study has been terminated.
(Study sponsor terminated study due to AE's reported with valsartan and aliskiren)
Sponsor:
Information provided by (Responsible Party):
Jonathan S. Williams, MD, MMSc, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01252238
First received: December 1, 2010
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

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 Intervention
Insulin Sensitivity
Aortic Compliance
Diastolic Function
Drug: Aliskiren
Drug: Valsartan and Aliskiren
Drug: Amlodipine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Renin Inhibition on Insulin Sensitivity, Diastolic Function and Aortic Compliance

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Change in Insulin Sensitivity by HOMA at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The difference (change) in HOMA calculated as Baseline HOMA minus 12-week HOMA value

  • Aortic Compliance [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Diastolic Function [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: June 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252238

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Jonathan Williams, MD Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Jonathan S. Williams, MD, MMSc, Jonathan Williams, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01252238     History of Changes
Other Study ID Numbers: 2010p001286
Study First Received: December 1, 2010
Results First Received: June 24, 2013
Last Updated: June 24, 2013
Health Authority: United States: Institutional Review Board (IRB)

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Valsartan
Amlodipine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on August 28, 2014