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

NCT04746495 | Withdrawn Phase 4 DMC FDA Drug

• 2 other identifiers: HUM001704181K23HL128909-01A1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Keywords

mineralocorticoid; mineralocorticoid receptor; aldosterone; eplerenone; blood pressure

Outcome Measures

Primary Outcomes (2)

• Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) Cycle threshold (Ct) value of mineralocorticoid receptor-regulated gene messenger ribonucleic acid (mRNA)

  Cycle threshold of urinary mRNA biomarker following treatment with placebo and following treatment with eplerenone will be measured using RT-qPCR.

  Week 6 (after first study treatment)

• RT-qPCR Ct value of mineralocorticoid receptor-regulated gene mRNA

  Cycle threshold of urinary mRNA biomarker following treatment with placebo and following treatment with eplerenone will be measured using RT-qPCR.

  Week 12 (after second study treatment)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Eplerenone

EXPERIMENTAL

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

Drug: Eplerenone 50mg

Interventions

Placebo 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.

Placebo

Eplerenone 50mg 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.

Eplerenone

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• J Brian Byrd, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: * 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: February 9, 2021
• Study Start: February 1, 2023
• Primary Completion: July 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: De-identified data will be deposited into a repository within 1 year of the conclusion of the study.
• Access Criteria: No additional access restrictions will be placed on the de-identified data, beyond those required by the repository to access or download the data.

Locations

US (1)