Hypoglycemia and the Mineralocorticoid Receptor

Hypoglycemia Clinical Trial

— HypoMR  

Official title:

Hypoglycemia and the Mineralocorticoid Receptor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01394627
• Other study ID #: 2010P002054
• Secondary ID: K24HL103845R01HL
• Status: Completed
• Phase: N/A
• First received: July 11, 2011
• Last updated: October 16, 2017
• Start date: January 2011
• Est. completion date: August 2016

Study information

• Verified date: October 2017
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoglycemia

Intervention

Drug:
• Eplerenone
100mg x 2
• Placebo

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Robert Wood Johnson Foundation

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in Inflammation	Change in interleukin-6	Baseline and 2 hours after hypoglycemia