Clinical Trial: The Role of Mineralocorticoid Receptors in Vascular Function

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Role of Mineralocorticoid Receptors in Vascular Function

Brief Summary: The purpose of this study is to figure out how decreasing the activity of 11-beta hydroxysteroid dehydrogenase (11-beta HSD) will affect your blood vessel function. 11-beta HSD, which is found in the kidneys and blood vessels, is a natural protein that when active helps to keep your blood pressure under control.

Detailed Summary:

This study intends to determine whether activation of mineralocorticoid receptors affects vascular function. Vascular function relies on two components of the blood vessel: the inner lining (endothelium) and the vascular smooth muscle. In specific aim 1, we seek to determine if that inhibition of the enzyme 11-beta hydroxysteroid dehydrogenase (11-beta-HSD) will impair endothelium-dependent vasodilation and/or vascular smooth muscle function.

The syndrome of apparent mineralocorticoid excess (AME) is a rare disorder identified in approximately 50 individuals characterized by low-aldosterone hypertension, associated with low renin and hypokalemia These subjects avidly retain salt and water, have suppression of both plasma renin and aldosterone levels, but clinically appear as though they have a state of mineralocorticoid excess. A detailed series of investigations has elucidated the cause of this syndrome: severe attenuation of the enzyme 11 beta-hydroxysteroid dehydrogenase (11-beta-HSD). 11-beta-HSD converts cortisol, able to activate mineralocorticoid receptors to cortisone, which cannot. This abnormality can be identified by measuring an abnormal ratio of urinary breakdown products of cortisol and cortisone. Subjects with AME have a high ratio indicative of elevated cortisol concentrations.

Although classical AME is a rare syndrome with a specific recessive inheritance, several other mutations have been identified which cause a varying severity of disease. Recent evidence has suggested mild abnormalities in this pathway may be much more common. In fact two studies have demonstrated that subjects with essential hypertension had greater levels of cortisol/cortisone urinary levels than matched controls. Thus, mild abnormalities of this enzyme may be an important contributor to a segment of patients with high blood pressure
Sponsor: Brigham and Women's Hospital

Current Primary Outcome: Forearm Blood Flow [ Time Frame: Outcome was measured at the end of each study period (i.e. 14 days after Baseline measurements were taken) ]

At the end of each 14-day intervention (Glycyrrhinitic acid or Placebo), vascular endothelial function was assessed by measuring forearm blood flow and comparing to Baseline. The outcome measure depicted below reflects the change in forearm blood flow from Baseline after completing the glycyrrhinitic acid regimen as well as the change in forearm blood flow from Baseline after taking the matching placebo.


Original Primary Outcome: To determine that inhibition of the enzyme 11-beta hydroxysteroid dehydrogenase (11-beta-HSD) will impair vascular smooth muscle function and endothelial function [ Time Frame: one testing visit every month for 2 months ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Brigham and Women's Hospital

Dates:
Date Received: September 24, 2008
Date Started: February 2002
Date Completion:
Last Updated: September 14, 2016
Last Verified: September 2016