Hypoglycemia and the Mineralocorticoid Receptor (HypoMR)

The purpose of this study is to look at whether blockade of the mineralocorticoid receptor will result in changes in the cardiovascular and inflammatory response to hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia
• Intervention / Treatment: Drug: Placebo; Drug: Eplerenone

Detailed Description

The effect of ongoing hypoglycemia on cardiovascular autonomic function is unclear and the focus of this protocol. In our preliminary studies, the investigators demonstrated that baroreflex sensitivity is impaired during hypoglycemia in healthy individuals. Treatment with eplerenone (200mg total administered in two doses in the 15 hours prior to the hypoglycemic clamp) prevented this impairment.

The study is based on the overarching hypothesis that hypoglycemia leads to increases in aldosterone/mineralocorticoid receptor (MR) activity and increased cardiovascular injury.

This study will address the following Specific Aims:

To test the hypothesis that MR blockade will reduce the adverse effects of hypoglycemia on inflammation and on autonomic control of cardiovascular function.

The investigators will determine the effects of hypoglycemia (50 mg/dl for 2.0 hours) on the blood inflammatory factor interleukin-6 levels, and on cardiovascular autonomic function (baroreflex sensitivity) in each subject under two conditions - pretreatment with MR blockade (eplerenone) and pretreatment with placebo.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Males and females age 18 to 40 years

Exclusion Criteria:

• Pregnancy
• Lactation
• Menopause
• Any medical condition other than treated hypothyroidism.
• Alcoholism
• Active tobacco use
• In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded.
• Use of medications other than physiological thyroxine replacement
• Serum potassium >5.0 mmol/L
• Estimated glomerular filtration rate < 60 mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eplerenone; hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose)	Drug: Eplerenone; 100mg x 2
Placebo Comparator: placebo; hypoglycemia of 50 mg/dl plus placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cardiovascular Autonomic Function	Modified oxford procedures was performed in duplicate immediately prior to start of the hypoglycemic clamp and during the last 30 min of the clamp (i.e. during the last 30 min of exposure to 2 hours of hypoglycemia).. We calculated the baroreflex sensitivity (the relationship between RR interval and change in systolic blood pressure defined as the change in the inter-beat cardiac interval in milliseconds per unit change in blood pressure in mmHg) at each time point and then the change in baroreflex sensitivity (BRS during hypoglycemia minus BRS at baseline)	Baseline and 2 hours after hypoglycemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Inflammation	Change in interleukin-6	Baseline and 2 hours after hypoglycemia

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); Robert Wood Johnson Foundation
• Investigators: Principal Investigator: Gail K Adler, MD, Brigham and Women's Hospital; Principal Investigator: Gail K Adler, MD, PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Rao AD, Bonyhay I, Dankwa J, Baimas-George M, Kneen L, Ballatori S, Freeman R, Adler GK. Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control. Diabetes. 2016 Jan;65(1):209-15. doi: 10.2337/db15-0871. Epub 2015 Oct 5.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 13, 2011
• First Posted (Estimate): July 14, 2011

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 2010P002054; K24HL103845 (U.S. NIH Grant/Contract); T32HL007609 (U.S. NIH Grant/Contract); R01HL109634 (U.S. NIH Grant/Contract)