Systemic Proinflammatory State
Conditions
Brief summary
The purpose of this study is to investigate the effect of mineralocorticoid receptor (MR) blockade in healthy participants in a systemic proinflammatory state after a meal high in fat and glucose, which is associated with the pathogenesis of atherosclerosis. Participants will include normal-weight, healthy males (Body Mass Index (BMI) ≤ 25 kg/m\^2) between the ages of 18-45, without hypertension and clinical evidence of metabolic, cardiovascular or any other kind of diseases. After a 12-hour (h) fast, participants will be assigned to a combination of oral fat-loading test (OFLT) and oral glucose tolerance test (OGTT) (day 1), followed by a two-week treatment with 50 mg eplerenone. After two weeks, participants will receive the second OFLT/OGTT treatment (day 15). Starting 5 days prior to the first intervention (day1), the participant's usual diet (ad lib) will be supplemented with 2 bullion broths each day. Standardization of sodium intake is necessary as variations in dietary sodium intake may affect outcome measures. We will evaluate the following parameters at day 1 and day 15 of the study. Prior to OFLT/OGTT, and 2h, 4h thereafter, we will measure a parameter of vascular and systemic inflammation: interleukin-6 (IL-6).
Interventions
DRUGEplerenone
50 mg daily for 14 days
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* male * 18-45 years * BMI between 20-25 kg/m\^2
Exclusion criteria
* evidence of cardiovascular, hepatic, renal \[estimated glomerular filtration rate (GFR) \<60 millimeter/minute (ml/min)\] or any other organ system disease * Blood pressure equal to or less than 90/60 mmHg * prescription or herbal medications * smoking * alcohol consumption of more than 2 drinks per day * dietary supplements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment | At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-prandial Glucose Serum Levels | Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment | At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days. |
| Post-prandial Insulin Serum Levels | Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment | At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eplerenone Eplerenone 50 mg daily for 14 days | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participant withdrew consent | 2 |
Baseline characteristics
| Characteristic | Eplerenone |
|---|---|
| Age, Continuous | 25 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels
At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days.
Time frame: Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment
Population: Data reported for evaluable participants only. All participants who completed the study and had glucose data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Pre-eplerenone, baseline | 1.70 ng/mL | Standard Deviation 0.93 |
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Pre-eplerenone, 2 hours | 1.51 ng/mL | Standard Deviation 0.73 |
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Pre-eplerenone, 4 hours | 1.65 ng/mL | Standard Deviation 0.79 |
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Post-eplerenone, baseline | 1.78 ng/mL | Standard Deviation 0.85 |
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Post-eplerenone, 2 hours | 1.47 ng/mL | Standard Deviation 0.93 |
| Eplerenone | Vascular and Systemic Inflammation as Measured by Interleukin-6 (IL-6) Serum Levels | Post-eplerenone, 4 hours | 1.75 ng/mL | Standard Deviation 0.96 |
Secondary
Post-prandial Glucose Serum Levels
At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days.
Time frame: Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment
Population: Data reported for evaluable participants only. All participants who completed the study and had glucose data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Post-prandial Glucose Serum Levels | Pre-eplerenone, baseline | 91 mg/dl | Standard Deviation 7 |
| Eplerenone | Post-prandial Glucose Serum Levels | Pre-eplerenone, 2 hours | 105 mg/dl | Standard Deviation 28 |
| Eplerenone | Post-prandial Glucose Serum Levels | Pre-eplerenone, 4 hours | 93 mg/dl | Standard Deviation 17 |
| Eplerenone | Post-prandial Glucose Serum Levels | Post-eplerenone, baseline | 89 mg/dl | Standard Deviation 12 |
| Eplerenone | Post-prandial Glucose Serum Levels | Post-eplerenone, 2 hours | 102 mg/dl | Standard Deviation 21 |
| Eplerenone | Post-prandial Glucose Serum Levels | Post-eplerenone, 4 hours | 92 mg/dl | Standard Deviation 20 |
Secondary
Post-prandial Insulin Serum Levels
At Visit 1, blood was drawn before and then 2h and 4h after a high-fat/high-glucose meal (50 g fat, 75 g glucose). Participants then followed a low-dose eplerenone treatment (50 mg daily) for 14 days. At Visit 2, blood was drawn again before, 2h, and 4h after a high-fat/high-glucose meal after 14 days.
Time frame: Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment
Population: Data reported for evaluable participants only. All participants who completed the study and had glucose data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Post-prandial Insulin Serum Levels | Pre-eplerenone, baseline | 4.5 uU/ml | Standard Deviation 3.6 |
| Eplerenone | Post-prandial Insulin Serum Levels | Pre-eplerenone, 2 hours | 33.0 uU/ml | Standard Deviation 45.7 |
| Eplerenone | Post-prandial Insulin Serum Levels | Pre-eplerenone, 4 hours | 10.4 uU/ml | Standard Deviation 10.7 |
| Eplerenone | Post-prandial Insulin Serum Levels | Post-eplerenone, baseline | 5.7 uU/ml | Standard Deviation 8.7 |
| Eplerenone | Post-prandial Insulin Serum Levels | Post-eplerenone, 2 hours | 23.2 uU/ml | Standard Deviation 21.5 |
| Eplerenone | Post-prandial Insulin Serum Levels | Post-eplerenone, 4 hours | 8.7 uU/ml | Standard Deviation 6.2 |