Hypertension
Conditions
Keywords
mineralocorticoid, mineralocorticoid receptor, aldosterone, eplerenone, blood pressure
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.
Interventions
DRUGPlacebo
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.
DRUGEplerenone 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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, 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
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed