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

Sponsor

University of Michigan (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04746495

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Placebo Drug: Eplerenone 50mg	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Lab results will be reviewed by an un-blinded co-investigator. Dose adjustments will be done by an un-blinded co-investigator who is licensed to prescribe the study drug. The study blind will be broken on completion of the clinical study.

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will be randomized to receive 4 weeks of placebo and then 4 weeks of Eplerenone.	Drug: 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.
Experimental: Eplerenone Participants will be randomized to receive 4 weeks of Eplerenone and then 4 weeks of Placebo.	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.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

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

Drug: 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.

Experimental: Eplerenone

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

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.

Outcome Measures

Primary Outcome Measures

Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) Cycle threshold (Ct) value of mineralocorticoid receptor-regulated gene messenger ribonucleic acid (mRNA) [Week 6 (after first study treatment)]
Cycle threshold of urinary mRNA biomarker following treatment with placebo and following treatment with eplerenone will be measured using RT-qPCR.
RT-qPCR Ct value of mineralocorticoid receptor-regulated gene mRNA [Week 12 (after second study treatment)]
Cycle threshold of urinary mRNA biomarker following treatment with placebo and following treatment with eplerenone will be measured using RT-qPCR.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

History of mild stage 1 systemic hypertension as defined by:

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