Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)

NCT ID: NCT04746495

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-28
• Study Completion Date: 2023-12-01

Brief Summary

This blinded cross-over clinical trial will enroll participants with mild stage 1 hypertension to evaluate whether urinary extracellular transcript abundance predicts response to an mineralocorticoid receptor (MR) antagonist, eplerenone.

Eligible participants will have a 2 week wash-in period followed by 4 weeks of treatment with placebo or eplerenone. There will be a 2 week wash out period from study medications and then participants will take the other drug (placebo or eplerenone) for 4 weeks. In addition, participants will also provide urine and blood samples during the trial, have physical assessments, and be monitored for safety.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants will be randomized to receive 4 weeks of placebo and then 4 weeks of Eplerenone.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will go through a 2-week wash-in period. During the wash-in period, the participant will be asked not to take their usual antihypertensive medications for their mild hypertension. After the 2-week wash-in period, the participants will begin a 4-week treatment period and will take a placebo once a day for 4 weeks. After the 4 weeks, the participants will have a 2-week wash-out period where they will be off the study treatment. After the 2-week wash-out period, the participants will begin the Eplerenone treatment for another 4 weeks.

Eplerenone

Participants will be randomized to receive 4 weeks of Eplerenone and then 4 weeks of Placebo.

Group Type: EXPERIMENTAL

Eplerenone 50mg

Intervention Type: DRUG

Participants will go through a 2-week wash-in period. During the wash-in period, the participant will be asked not to take their usual antihypertensive medications for their mild hypertension. After the 2-week wash-in period, the participants will begin a 4-week treatment period of Eplerenone for 4 weeks. After the 4 weeks, the participants will have a 2-week wash-out period where they will be off the study treatment. After the 2-week wash-out period, the participants will then begin the Placebo treatment for another 4 weeks.

Interventions

Placebo

Participants will go through a 2-week wash-in period. During the wash-in period, the participant will be asked not to take their usual antihypertensive medications for their mild hypertension. After the 2-week wash-in period, the participants will begin a 4-week treatment period and will take a placebo once a day for 4 weeks. After the 4 weeks, the participants will have a 2-week wash-out period where they will be off the study treatment. After the 2-week wash-out period, the participants will begin the Eplerenone treatment for another 4 weeks.

Intervention Type: DRUG

Eplerenone 50mg

Participants will go through a 2-week wash-in period. During the wash-in period, the participant will be asked not to take their usual antihypertensive medications for their mild hypertension. After the 2-week wash-in period, the participants will begin a 4-week treatment period of Eplerenone for 4 weeks. After the 4 weeks, the participants will have a 2-week wash-out period where they will be off the study treatment. After the 2-week wash-out period, the participants will then begin the Placebo treatment for another 4 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• History of mild stage 1 systemic hypertension as defined by:

1. Systolic blood pressure (SBP) ≥ 140 millimeters of Mercury (mmHg) or diastolic blood pressure (DBP) ≥ 90 mmHg on 2 occasions and

2. Treatment with 1-2 antihypertensive medications (stable dose for 6 weeks)

Exclusion Criteria

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• Stage 2 hypertension (history of blood pressure ≥ 160/100 mmHg)
• History of hypertensive urgency, hypertensive crisis, or hospitalizations for hypertension
• Current mineralocorticoid antagonist use
• Type II Diabetes with microalbuminuria
• Primary adrenal insufficiency
• Current glucocorticoid use
• Electrolyte abnormality on baseline laboratory assessment
• Current potassium supplementation
• Positive test for leukocyte esterase on urinalysis
• Creatinine clearance < 50 mL/min on baseline laboratory assessment
• Hyperkalemia
• Potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene)
• Serum potassium >5.0 milliequivalents per liter (mEq/L) on baseline laboratory assessment
• Current use of strong CYP3A4 inhibitors (some include: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir).
• Serum creatinine > 1.5 mg/dL in males on baseline laboratory assessment
• Serum creatinine > 1.3 mg/dL in females
• Current beta blocker use
• Any other condition thought by the Principal Investigator to place the participant at increased risk of injury during the clinical trial or compromise the scientific integrity of the study

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

J Brian Byrd, MD, MS

Assistant Professor of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J Brian Byrd, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

1K23HL128909-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00170418

Identifier Type: -

Identifier Source: org_study_id