Assessment of Renin Inhibition on Insulin Sensitivity, Diastolic Function and Aortic Compliance
|ClinicalTrials.gov 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
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:
- 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.
- 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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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.
Aliskiren 150 mg daily for 10 weeks, force titrated after initial 2 weeks.
Placebo Comparator: Placebo Group
Only taking Amlodipine
Taking Amlodipine as prescribed by MD for management of high blood pressure.
- 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
- Aortic Compliance [ Time Frame: 12 weeks ]Characteristic aortic imedeance, dynes x s/cm5
- Pulse Wave Velocity [ Time Frame: 12 weeks ]Measure of pulsewave velocity cm/s
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01252238
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Jonathan Williams, MD||Brigham and Women's Hospital|