Clinical trial NCT04746495: Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)
Official title: Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Hypertension
Keywords: mineralocorticoid
mineralocorticoid receptor
aldosterone
eplerenone
blood pressure
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-02-09
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) Cycle threshold (Ct) value of mineralocorticoid receptor-regulated gene messenger ribonucleic acid (mRNA)
timeFrame: Week 6 (after first study treatment)
measure: RT-qPCR Ct value of mineralocorticoid receptor-regulated gene mRNA
timeFrame: Week 12 (after second study treatment)
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: J Brian Byrd, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: