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

Hypertension Clinical Trial

— ENOVA  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04746495
• Other study ID #: HUM00170418
• Secondary ID: 1K23HL128909-01A
• Status: Withdrawn
• Phase: Phase 4
• Start date: February 2023
• Est. completion date: December 1, 2023

Study information

• Verified date: February 2023
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Placebo
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.
• Eplerenone 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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)