Back to results

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

Primary Purpose

Hypertension

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Placebo

Eplerenone 50mg

About this trial

This is an interventional basic science trial for Hypertension focused on measuring mineralocorticoid, mineralocorticoid receptor, aldosterone, eplerenone, blood pressure

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Eplerenone

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04746495

First Posted

January 12, 2021

Last Updated

February 16, 2023

Sponsor

University of Michigan

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT04746495

Brief Title

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

Acronym

ENOVA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Issues relate to COVID-19 and staffing challenges, as well as very tight finances.

Study Start Date

February 2023 (Anticipated)

Primary Completion Date

July 1, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension

Keywords

mineralocorticoid, mineralocorticoid receptor, aldosterone, eplerenone, blood pressure

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

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.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Eplerenone

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Eplerenone 50mg

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Week 6 (after first study treatment)

Title

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

Description

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

Time Frame

Week 12 (after second study treatment)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

J Brian Byrd, MD, MS

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

We will de-identify participant information and will share it with a trusted repository, such as National Institutes of Health (NIH) Figshare or The Inter-university Consortium for Political and Social Research (ICPSR). We will de-identify and share data obtained from analyzing urinary mRNA biomarkers and measuring the systolic and diastolic blood pressure following consumption of a high-sodium and low-sodium diet. Additionally, specific lab values that support the validity and quality of the study treatment will be shared in a trusted repository.

IPD Sharing Time Frame

De-identified data will be deposited into a repository within 1 year of the conclusion of the study.

IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs