Recruiting

Phase 2

Phase 3

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

Sponsor:

University of Alabama at Birmingham

Code:

NCT04971720

Conditions

Obesity

Cardiovascular Diseases

Hypertension

Nocturnal Blood Pressure

Natriuretic Peptides

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Interventions

Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet

Valsartan 80 mg Oral Tablet

Study Details

Brief 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

Study ID

NCT04971720

Start date

Feb 18, 2022

Status verified date

Apr, 2026

Completion date

Jan 1, 2027

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Inclusion Criteria:

Age more than or equal to 18 years of age
Body Mass Index between 30 to 45 kg/m\^2
Blood pressure: Systolic BP more than or equal to 130mmHg and less than or equal to 160mmHg and diastolic blood pressure more than or equal to 80mmHg and less than or equal to 100mmHg. Individuals with hypertension as per the 2017 ACC/AHA Guidelines will be eligible for enrollment

Exclusion Criteria:

Age less than 18, at screening.
Systolic BP <130 or >160mmHg at baseline, or diastolic BP <80 or >100 mmHg at baseline
BMI <30 kg/m\^2 or >45 kg/m\^2
History of pulmonary hypertension
Have any past or present illness of cardiovascular disease including myocardial infarction, angina, cardiac arrhythmia, diabetes, stroke, TIA, or seizure.
Participants who are taking 3 or more classes of hypertension medications on the maximum dose or with resistant hypertension
History of angioedema
Estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 (CKD-EPI equation); urine albumin creatinine ratio ≥30 mg/g
Hepatic Transaminase (AST and ALT) levels >3x the upper limit of normal;
Significant psychiatric illness
Anemia (men, Hct < 38%; women, Hct <36%)
Participants working night shifts or swing shifts
Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence)

Study Design

Enrollment

160 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Sacubitril/Valsartan Morning Dose

We will enroll 40 adult obese individuals. Each participant will take the assigned dose of medication once in the morning and a placebo pill in the evening for 28 days. We evaluate Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure at baseline and after 28 days of intervention.

experimental: Sacubitril/Valsartan Evening Dose

We will enroll 40 adult obese individuals. Each participant will take the assigned dose of medication once in the evening and a placebo pill in the morning for 28 days. We evaluate Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure at baseline and after 28 days of intervention.

active comparator: Valsartan Morning Dose

active comparator: Valsartan Evening Dose

Interventions

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.

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.

Primary outcome measure

Change in mean nocturnal systolic blood pressure [ Time Frame: At Baseline and after 28 days of intervention. ]

Central Contacts and Locations

Central contacts

Nehal Vekariya, MS

205-934-7173 nvekariya@uabmc.edu

Deborah Weber, BSN, RN

205-975-9964 dlowe@uabmc.edu

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Contacts

Nehal Vekariya, MS

205-934-7173 nvekariya@uabmc.edu

Principal Investigator:

Pankaj Arora, MD

More Information

Sponsor

University of Alabama at Birmingham

Last update posted

Apr 9, 2026

Last verified

Apr, 2026

Keywords

Natriuretic Peptides
Nocturnal Blood Pressure
Renin-Angiotensin-Aldosterone System
Obesity

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Alabama at Birmingham on 2026-04-09.