Effect of Eplerenone on Postprandial Inflammatory Response in Healthy Adults

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).

Study Overview

• Status: Completed
• Conditions: Systemic Proinflammatory State
• Intervention / Treatment: Drug: Eplerenone

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eplerenone; Eplerenone 50 mg daily for 14 days	Drug: Eplerenone; 50 mg daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment
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.	Baseline, 2 hours, and 4 hours, measured before and after 2 weeks of eplerenone treatment

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Gail K Adler, MD, PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Krug AW, Stelzner L, Rao AD, Lichtman AH, Williams GH, Adler GK. Effect of low dose mineralocorticoid receptor antagonist eplerenone on glucose and lipid metabolism in healthy adult males. Metabolism. 2013 Mar;62(3):386-91. doi: 10.1016/j.metabol.2012.08.011. Epub 2012 Sep 21.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: February 4, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 2010P002191