Clinical trial NCT01394627: Hypoglycemia and the Mineralocorticoid Receptor
Official title: Hypoglycemia and the Mineralocorticoid Receptor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypoglycemia
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Robert Wood Johnson Foundation
name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-07-14
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Cardiovascular Autonomic Function
timeFrame: Baseline and 2 hours after hypoglycemia
Secondary outcomes:
measure: Change From Baseline in Inflammation
timeFrame: Baseline and 2 hours after hypoglycemia
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Gail K Adler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Gail K Adler, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.