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

Phase 4

Withdrawn

• Conditions: Hypertension
• Interventions: Drug: Eplerenone 50mg; Drug: Placebo

• Registration Number: NCT04746495
• Lead Sponsor: University of Michigan

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-12
• Study First Submitted QC: 2021-02-05
• Study First Posted: 2021-02-09
• Status Verified: 2023-02
• Study Start: 2023-02
• Last Update Submitted: 2023-02-16
• Last Update Posted: 2023-02-21
• Primary Completion: 2023-07-01
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Eplerenone	Eplerenone 50mg	Participants will be randomized to receive 4 weeks of Eplerenone and then 4 weeks of Placebo.
Placebo	Placebo	Participants will be randomized to receive 4 weeks of placebo and then 4 weeks of Eplerenone.

Primary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States