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

NCT01252238 | Terminated Results

• 1 other identifier: 2010p001286
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Insulin Sensitivity; Aortic Compliance; Diastolic Function

Outcome Measures

Primary Outcomes (1)

• Change in Insulin Sensitivity by HOMA at 12 Weeks

  The difference (change) in HOMA calculated as Baseline HOMA minus 12-week HOMA value

  12 weeks

Secondary Outcomes (1)

• Aortic Compliance

  12 weeks

Other Outcomes (1)

• Pulse Wave Velocity

  12 weeks

Study Arms (3)

Valsartan and Aliskiren

PLACEBO COMPARATOR

Valsartan 150 mg and Aliskiren (150 mg followed by force titration to 300 mg)

Drug: Valsartan and Aliskiren

Aliskiren

EXPERIMENTAL

Drug: Aliskiren

Placebo Group

PLACEBO COMPARATOR

Only taking Amlodipine

Drug: Amlodipine

Interventions

Aliskiren DRUG

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

Aliskiren

Valsartan and Aliskiren DRUG

Subject taking combination of valsartan and aliskiren.

Valsartan and Aliskiren

Amlodipine DRUG

Taking Amlodipine as prescribed by MD for management of high blood pressure.

Placebo Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

aliskiren; Valsartan; Amlodipine

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines

Limitations and Caveats

No conclusions can be drawn from study due to very low sample size. The sponsor terminated the study after a separate study reported adverse events in a diabetic population who had taken both valsartan and aliskiren.

Results Point of Contact

• Title: Dr. Jonathan Williams
• Organization: Brigham and Women's Hospital

jwilliams5@partners.org

617-278-0882

Study Officials

• Jonathan Williams, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jonathan Williams, MD

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 2, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 13, 2018
• Results First Posted: September 5, 2013

Record last verified: 2018-01

Locations

US (1)