AzTrials
AzTrials

ObesityPhase 2/3PRECISION-BPNCT04971720

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

A Phase 2/3 study testing Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet and Valsartan 80 mg Oral Tablet in people with Obesity and Cardiovascular Diseases, run by University of Alabama at Birmingham at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Obesity, Cardiovascular Diseases, Hypertension
What is being tested?
Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet and Valsartan 80 mg Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
1 siteUnited States
Study dates
18 Feb 2022to 1 Jan 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Nehal Vekariya, MS contact

205-934-7173

nvekariya@uabmc.edu

Deborah Weber, BSN, RN contact

205-975-9964

dlowe@uabmc.edu

United States1 site, 1 recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Nehal Vekariya, MS, 205-934-7173, nvekariya@uabmc.edu

    Pankaj Arora, MD

    Recruiting

Other trials in United States

About this study

Official title: Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure

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.

Read the detailed description

The investigators have demonstrated that there exists a diurnal rhythm of natriuretic peptides (NPs) which tracks closely with the BP rhythm and is in an antiphase relationship with the rhythm of the RAAS (Renin-Angiotensin-Aldosterone System) hormones. The NP levels are lowest at night, and the renin and aldosterone levels are highest at nighttime. Furthermore, the investigators have demonstrated that obese individuals have a putative deficiency of NPs, and this is due to decreased production alongside increased clearance of NPs. LCZ696 is an FDA-approved inhibitor of neprilysin (an NP degrading enzyme) that augments the NP levels and also suppresses the RAAS. Hence, the confluence of putative NP deficiency among obese alongside the lower levels of NPs at nighttime and the increased activity of RAAS at night may contribute to the high-risk nocturnal non-dipping BP profile among obese individuals. Chronopharmacology (controlling the time of medication administration) to synchronize the NP-RAAS axis targeting anti-hypertensive medications with the inherent biological NP-RAAS-BP rhythm axis may help in controlling the high-risk nocturnal BP non-dipping in obese. Investigators hypothesize that nighttime administration of NP augmenting and/or RAAS inhibition therapy in obese hypertensive individuals will help to improve their nocturnal BP rhythm. The investigators aim to conduct a patient-oriented physiological clinical trial to assess the effect of timing of administration of NP-RAAS axis therapy on restoring the normal BP rhythm. This study is a 2x2 factorial design trial, wherein individuals will be randomized to either daytime dosing or nighttime dosing of either LCZ696 or valsartan. The investigators will study the effect of timing of NP augmenting and/or RAAS inhibiting therapy on the nighttime BP profile in obese hypertensive patients with nondipping nocturnal BP. The investigators will also assess the effect of NP augmentation in an NP deficient population on the nocturnal BP profile, i.e., in obese hypertensives with nondipping nocturnal BP. The investigators will also examine the impact of NP augmenting-RAAS inhibiting therapy on the NP levels and the physiological diurnal rhythms.

This study will assess the physiological implications of chronopharmacology of anti-hypertensive therapy and assess a potentially novel approach of using the inherent biological rhythms to reduce the normal BP rhythmicity in a high-risk population

Being tested
Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet, Valsartan 80 mg Oral Tablet
Keywords
Natriuretic Peptides, Nocturnal Blood Pressure, Renin-Angiotensin-Aldosterone System, Obesity
Medical subject headings
Obesity, Cardiovascular Diseases, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sacubitril-Valsartan 49 Mg-51 Mg Oral TabletDrug

    Also called Sacubitril/Valsartan

    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 TabletDrug

    Also called Valsartan

    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.

Study groups in NCT04971720
Study groupRoleWhat they receive
Sacubitril/Valsartan Morning DoseExperimentalWe 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.
Receives: Drug: Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet
Sacubitril/Valsartan Evening DoseExperimentalWe 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.
Receives: Drug: Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet
Valsartan Morning DoseActive comparatorWe 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.
Receives: Drug: Valsartan 80 mg Oral Tablet
Valsartan Evening DoseActive comparatorWe 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.
Receives: Drug: Valsartan 80 mg Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At Baseline and after 28 days of intervention.

Secondary outcomes (15)

  1. Change in percent nocturnal dipping blood pressure

    Change in percent nocturnal dipping 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.

    Measured: At Baseline and after 28 days of intervention.

  2. Change in 24-hour mean systolic blood pressure

    Change in 24-hour mean 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.

    Measured: At Baseline and after 28 days of intervention.

  3. Change in 24-hour mean diastolic blood pressure

    Change in 24-hour mean diastolic 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.

    Measured: At Baseline and after 28 days of intervention.

  4. Change in mean daytime systolic blood pressure

    Change in mean daytime 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.

    Measured: At Baseline and after 28 days of intervention

  5. Change in mean daytime diastolic blood pressure

    Change in mean daytime diastolic 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.

    Measured: At Baseline and after 28 days of intervention

  6. Change in mean nocturnal diastolic blood pressure

    Change in mean nocturnal diastolic 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.

    Measured: At Baseline and after 28 days of intervention.

  7. Change in the daytime, nocturnal, and total urinary excretion parameters (Urine Sodium, Urine Potassium, Urine Creatinine, Urine Albumin).

    Change in the daytime, nocturnal, and total urinary excretion parameters (Urine Sodium, Urine Potassium, Urine Creatinine, Urine Albumin) 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.

    Measured: At Baseline and after 28 days of intervention

  8. Change in 24-hour, daytime, and nocturnal ANP, BNP, NTproBNP, and renin levels

    Change in 24-hour, daytime, and nocturnal ANP, BNP, NTproBNP, and renin levels 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.

    Measured: At Baseline and after 28 days of intervention

  9. Change in 24-hour, daytime, and nocturnal MRproANP levels

    Change in 24-hour, daytime, and nocturnal MRproANP levels 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.

    Measured: At Baseline and after 28 days of intervention

  10. Change in 24-hour, daytime, and nocturnal Aldosterone levels

    Change in 24-hour, daytime, and nocturnal Aldosterone levels 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.

    Measured: At Baseline and after 28 days of intervention

  11. Change in rhythm parameters (mesor, amplitude, and phase) for ANP, BNP, NTproBNP, renin, and melatonin rhythms.

    Change in rhythm parameters (mesor, amplitude, and phase) for ANP, BNP, NTproBNP, renin, and melatonin rhythms 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.

    Measured: At Baseline and after 28 days of intervention

  12. Change in rhythm parameters (mesor, amplitude, and phase) for MRproANP.

    Change in rhythm parameters (mesor, amplitude, and phase) for MRproANP 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.

    Measured: At Baseline and after 28 days of intervention

  13. Change in rhythm parameters (mesor, amplitude, and phase) for aldosterone rhythms.

    Change in rhythm parameters (mesor, amplitude, and phase) for aldosterone rhythms 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.

    Measured: At Baseline and after 28 days of intervention

  14. Change in rhythm parameters (mesor, amplitude, and phase) for cortisol rhythms.

    Change in rhythm parameters (mesor, amplitude, and phase) for cortisol rhythms 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.

    Measured: At Baseline and after 28 days of intervention

  15. Change in rhythm parameters (mesor, amplitude, and phase) for systolic BP, and diastolic BP rhythms.

    Change in rhythm parameters (mesor, amplitude, and phase) for systolic BP, and diastolic BP rhythms 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.

    Measured: At Baseline and after 28 days of intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2021
  2. Study start18 Feb 2022
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Other
Allocation
Randomised
Intervention model
Factorial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04971720
Sponsor's protocol ID
IRB-300007789
Other IDs
R01HL160982
Acronym
PRECISION-BP
Status last verified
Apr 2026
First submitted
12 Jul 2021
Last updated
9 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 33958126

  • 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.

    PubMed 26892417

  • 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.

    PubMed 29167879

  • 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.

    PubMed 25595796

  • 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.

    PubMed 33624057

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sacubitril-Valsartan 49 Mg-51 Mg Oral Tablet and Valsartan 80 mg Oral Tablet in people with Obesity and Cardiovascular Diseases, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nehal Vekariya, MS (205-934-7173, nvekariya@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in mean nocturnal systolic blood pressure (time frame: At Baseline and after 28 days of intervention.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04971720, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
PRECISION-BP Clinical Trial NCT04971720 | AzTrials