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

NCT04971720 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-300007789R01HL160982
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in mean nocturnal systolic blood pressure

  Change in mean nocturnal systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention.

  At Baseline and after 28 days of intervention.

Secondary Outcomes (15)

• Change in percent nocturnal dipping blood pressure

  At Baseline and after 28 days of intervention.

• Change in 24-hour mean systolic blood pressure

  At Baseline and after 28 days of intervention.

• Change in 24-hour mean diastolic blood pressure

  At Baseline and after 28 days of intervention.

• Change in mean daytime systolic blood pressure

  At Baseline and after 28 days of intervention

• Change in mean daytime diastolic blood pressure

  At Baseline and after 28 days of intervention

Study Arms (4)

Sacubitril/Valsartan Morning Dose

EXPERIMENTAL

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.

Drug: Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet

Sacubitril/Valsartan Evening Dose

EXPERIMENTAL

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.

Drug: Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet

Valsartan Morning Dose

ACTIVE COMPARATOR

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.

Drug: Valsartan 80 mg Oral Tablet

Valsartan Evening Dose

ACTIVE COMPARATOR

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.

Drug: Valsartan 80 mg Oral Tablet

Interventions

Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet DRUG

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.

Also known as: Sacubitril/Valsartan

Sacubitril/Valsartan Evening Dose; Sacubitril/Valsartan Morning Dose

Valsartan 80 mg Oral Tablet DRUG

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.

Also known as: Valsartan

Valsartan Evening Dose; Valsartan Morning Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Related Publications (5)

• Parcha V, Patel N, Gutierrez OM, Li P, Gamble KL, Musunuru K, Margulies KB, Cappola TP, Wang TJ, Arora G, Arora P. Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals. J Am Coll Cardiol. 2021 May 11;77(18):2291-2303. doi: 10.1016/j.jacc.2021.03.291.

  PMID: 33958126 BACKGROUND

• Arora P, Wu C, Hamid T, Arora G, Agha O, Allen K, Tainsh RET, Hu D, Ryan RA, Domian IJ, Buys ES, Bloch DB, Prabhu SD, Bloch KD, Newton-Cheh C, Wang TJ. Acute Metabolic Influences on the Natriuretic Peptide System in Humans. J Am Coll Cardiol. 2016 Feb 23;67(7):804-812. doi: 10.1016/j.jacc.2015.11.049.

  PMID: 26892417 BACKGROUND

• Bajaj NS, Gutierrez OM, Arora G, Judd SE, Patel N, Bennett A, Prabhu SD, Howard G, Howard VJ, Cushman M, Arora P. Racial Differences in Plasma Levels of N-Terminal Pro-B-Type Natriuretic Peptide and Outcomes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. JAMA Cardiol. 2018 Jan 1;3(1):11-17. doi: 10.1001/jamacardio.2017.4207.

  PMID: 29167879 BACKGROUND

• Arora P, Reingold J, Baggish A, Guanaga DP, Wu C, Ghorbani A, Song Y, Chen-Tournaux A, Khan AM, Tainsh LT, Buys ES, Williams JS, Heublein DM, Burnett JC, Semigran MJ, Bloch KD, Scherrer-Crosbie M, Newton-Cheh C, Kaplan LM, Wang TJ. Weight loss, saline loading, and the natriuretic peptide system. J Am Heart Assoc. 2015 Jan 16;4(1):e001265. doi: 10.1161/JAHA.114.001265.

  PMID: 25595796 BACKGROUND

• Parcha V, Kalra R, Li P, Oparil S, Arora G, Arora P. Nocturnal blood pressure dipping in treated hypertensives: insights from the SPRINT trial. Eur J Prev Cardiol. 2022 Feb 19;29(1):e25-e28. doi: 10.1093/eurjpc/zwaa125. No abstract available.

  PMID: 33624057 BACKGROUND

MeSH Terms

Conditions

Obesity; Cardiovascular Diseases; Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan; Tablets

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nehal Vekariya, MS

CONTACT

205-934-7173; nvekariya@uabmc.edu

Deborah Weber, BSN, RN

CONTACT

205-975-9964; dlowe@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Cardiovascular Disease, Department of Medicine

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: July 21, 2021
• Study Start: February 18, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)