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| ID | Type | Description | Link |
|---|---|---|---|
| K24HL103845 | U.S. NIH Grant/Contract | View source | |
| R01HL109634 | U.S. NIH Grant/Contract | View source | |
| T32HL007609 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Robert Wood Johnson Foundation | OTHER |
| National Institutes of Health (NIH) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eplerenone | Experimental | hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose) |
|
| placebo | Placebo Comparator | hypoglycemia of 50 mg/dl plus placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eplerenone | Drug | 100mg x 2 |
| |
| Placebo |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Inflammation | Change in interleukin-6 | Baseline and 2 hours after hypoglycemia |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gail K Adler, MD | Brigham and Women's Hospital | Principal Investigator |
| Gail K Adler, MD, PhD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26438610 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Period 1) /Washout (Period 2)/Eplerenone (Period 3) | hypoglycemia of 50 mg/dl with 1 day of placebo pretreatment then after 1-3 month washout hypoglycemia of 50 mg/dl with 1 day of eplerenone (100 mg x 2) pretreatment |
| FG001 | Eplerenone (Period 1) /Washout (Period 2)/Placebo (Period 3) | hypoglycemia of 50 mg/dl with 1 day of eplerenone (100 mg x 2) pretreatment then after 1-3 month washout hypoglycemia of 50 mg/dl with 1 day of placebo pretreatment |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
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| ||||||||||||||||||
| Washout (1-3 Months) |
| |||||||||||||||||||
| Second Intervention (1 Day) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | 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. | Posted | Mean | Standard Deviation | ms/mmHg | Baseline and 2 hours after hypoglycemia |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eplerenone | hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose) Eplerenone: 100mg x 2 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gail Adler | Brigham and Women's Hospital | 617-732-5661 | gadler@partners.org |
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077545 | Eplerenone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 |
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| Drug |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose) Eplerenone: 100mg x 2 |
| OG001 | Placebo | hypoglycemia of 50 mg/dl plus placebo Placebo |
|
|
| Secondary | Change From Baseline in Inflammation | Change in interleukin-6 | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline and 2 hours after hypoglycemia |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Placebo | hypoglycemia of 50 mg/dl plus placebo Placebo | 0 | 20 | 0 | 20 | 0 | 20 |
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| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |