Hypoglycemia
Conditions
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.
Interventions
DRUGEplerenone
100mg x 2
DRUGPlacebo
Sponsors
Robert Wood Johnson Foundation
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cardiovascular Autonomic Function | Baseline and 2 hours after hypoglycemia | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inflammation | Baseline and 2 hours after hypoglycemia | Change in interleukin-6 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (1 Day) | poor intravenous access | 0 | 1 |
| Washout (1-3 Months) | concurrent enrollment in another study | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 26.5 years STANDARD_DEVIATION 5.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 21 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
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)
Time frame: Baseline and 2 hours after hypoglycemia
Population: We included the 13 subjects who completed each arm, had usable baroreflex sensitivity data for both treatments (placebo and eplerenone), and achieved a blood sugar during hypoglycemia of less than or equal to 3.0 mmol/L for each clamp.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eplerenone | Change From Baseline in Cardiovascular Autonomic Function | -16.00 ms/mmHg | Standard Deviation 18.39 |
| Placebo | Change From Baseline in Cardiovascular Autonomic Function | -16.59 ms/mmHg | Standard Deviation 16.77 |
Secondary
Change From Baseline in Inflammation
Change in interleukin-6
Time frame: Baseline and 2 hours after hypoglycemia
Population: We included the 17 subjects who completed each arm and had interleukin-6 data for both arms (placebo and eplerenone). We calculated the change in IL-6 as IL-6 during hypoglycemia minus IL-6 at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eplerenone | Change From Baseline in Inflammation | 2.03 pg/ml | Standard Deviation 1.27 |
| Placebo | Change From Baseline in Inflammation | 2.61 pg/ml | Standard Deviation 2.63 |