PRECISION-BP: Precision Chronopharamacotherapy Targeting NP-RAAS-BP Rhythm Axis

Summary

Obese individuals have a higher prevalence of nocturnal hypertension and non-dipping blood pressure (BP). These conditions are associated with an increased risk of cardiovascular (CV) events and death. Natriuretic Peptides (NPs) are hormones produced by the heart which directly regulate BP by causing dilation of blood vessels and by removing sodium and water from the body. NPs have a 24-hour day-night rhythm and this controls the day-night rhythm of BP as well. The NP-BP rhythm relationship is broken down in obese individuals. Obese individuals also have lower circulating NP levels. Lower circulating levels of NPs and elevated renin hormone (a part of the Renin-Angiotensin-Aldosterone System \[RAAS\]) at nighttime may contribute to the high nocturnal blood pressure in obese individuals which puts them at a higher risk of developing CV events. This current study seeks to determine the biological implications of chronopharmacology for synchronizing NP-RAAS-based blood pressure therapy with the physiological diurnal rhythms to restore the normal diurnal rhythm of blood pressure in obese individuals.

Conditions

• Obesity
• Cardiovascular Diseases
• Hypertension
• Nocturnal Blood Pressure
• Natriuretic Peptides
• Renin-Angiotensin-Aldosterone System

Interventions

DRUG

Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet

The subject will be randomized, in a double-blind manner to sacubitril/valsartan 49/51 mg once in the morning or once in the evening for a period of 28 days.

DRUG

Valsartan 80 mg Oral Tablet

The subject will be randomized, in a double-blind manner to valsartan 80 mg once in the morning or once in the evening for a period of 28 days.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• University of Alabama at Birmingham

  lead OTHER

Principal Investigators

• Pankaj Arora, MD, FAHA · University of Alabama at Birmingham

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-02-18

Primary Completion

2027-01-01

Completion

2027-01-01

FDA Drug

Yes

Countries

• United States

Study Locations