Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)
Trial Snapshot
- Phase
- Phase 4
- Status
- Withdrawn
- Sponsor
- University of Michigan
- Locations
- 1
- Primary Endpoint
- RT-qPCR Ct value of mineralocorticoid receptor-regulated gene mRNA
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- 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.
Eligibility Criteria
- Ages
- 21 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Placebo
Participants will be randomized to receive 4 weeks of placebo and then 4 weeks of Eplerenone.
Intervention: Placebo (Drug)
Eplerenone
Participants will be randomized to receive 4 weeks of Eplerenone and then 4 weeks of Placebo.
Intervention: Eplerenone 50mg (Drug)
Outcomes
Primary Outcomes
RT-qPCR Ct value of mineralocorticoid receptor-regulated gene mRNA
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported
Investigators
J Brian Byrd, MD, MS
Assistant Professor of Internal Medicine
University of Michigan