Genetic Architecture of Natriuretic Peptides and Blood Pressure Response

NCT07118592 | Not Yet Recruiting DMC

• 1 other identifier: IRB-300015234
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Natriuretic peptides (NPs) are hormones produced by the heart and play an important role in maintaining cardiovascular health and have favorable metabolic benefits. Low NP levels are associated with an increased likelihood of the development of cardiometabolic diseases like diabetes and hypertension. NP levels are known to be highly heritable, with up to half of the differences in NP levels being explained by genetics. The investigators aim to describe the genetic architecture of NPs by examining the genetic variants associated with NPs, and generate and validate a polygenic score (PGS) for NPs. The investigators will use this NP PGS to examine the association of genetically determined NP levels with cardiometabolic and cardiovascular outcomes. The investigators will conduct a genotype-guided physiological clinical trial that aims to assess the genetic factors affecting NP levels and their impact on blood pressure and NP response to saline infusion, high-salt diet, and low-salt diet. These findings will help support personal medicine approaches to lower the increasing burden of hypertension in the United States.

Conditions

Hypertension (HTN); Cardiometabolic Diseases

Keywords

Hypertension; Natriuretic peptides; Polygenic risk score; Cardiometabolic diseases

Outcome Measures

Primary Outcomes (2)

• Change in 24h mean Systolic Blood Pressure (SBP)

  Difference in the change in 24h mean SBP following high and low salt diets, between the polygenic score groups.

  3 weeks

• Change in N-terminal pro-B-type Natriuretic Peptide (NTproBNP) (NTproBNP)

  Difference in the change in NTproBNP levels following high and low salt diets, between the the polygenic score groups.

  3 weeks

Secondary Outcomes (16)

• Change in 24h mean Diastolic Blood Pressure (DBP)

  3 weeks

• Change in Daytime Diastolic Blood Pressure (DBP)

  3 weeks

• Change in Nighttime Diastolic Blood Pressure (DBP)

  3 weeks

• Change in Daytime Systolic Blood Pressure (SBP)

  3 weeks

• Change in Nighttime Systolic Blood Pressure (SBP)

  3 weeks

Study Arms (2)

High Natriuretic Peptide Polygenic Score

EXPERIMENTAL

Active Comparator: High NP PGS Group

Dietary Supplement: Low Salt Diet; Dietary Supplement: High Salt Diet; Dietary Supplement: Saline Infusion

Low Natriuretic Peptide Polygenic Score

EXPERIMENTAL

Experimental: Low NP PGS Group

Dietary Supplement: Low Salt Diet; Dietary Supplement: High Salt Diet; Dietary Supplement: Saline Infusion

Interventions

Low Salt Diet DIETARY_SUPPLEMENT

8 days of diet with low salt content will be given to the study participants

High Natriuretic Peptide Polygenic Score; Low Natriuretic Peptide Polygenic Score

High Salt Diet DIETARY_SUPPLEMENT

8 days of diet with high salt content will be given to the study participants

High Natriuretic Peptide Polygenic Score; Low Natriuretic Peptide Polygenic Score

Saline Infusion DIETARY_SUPPLEMENT

2 Liters of normal saline infusion (0.25 ml/kg/min over 2 hours) will be given to the study participants at the end of each study period

High Natriuretic Peptide Polygenic Score; Low Natriuretic Peptide Polygenic Score

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
• Consenting to collection of genetic material and willing to adhere to study protocol
• Stage I/II Hypertension (Systolic blood pressure: 130-159 and Diastolic blood pressure: 80-99 mm Hg)

You may not qualify if:

• Body mass index (BMI) more than 45 kg/m2
• History of uncontrolled hypertension (i.e., Systolic blood pressure more than or equal to 160 mmHg and/or Diastolic blood pressure more than or equal to 100 mmHg)
• If taking more than or equal to 2 blood pressure medications at the time of screening
• Systolic blood pressure more than 180 and/or Diastolic blood pressure more than or equal to 120 mmHg at any point in the study
• Present or past history of major cardiovascular disease including myocardial infarction, angina, cardiac arrhythmia, heart failure, stroke, transient ischemic attack, or seizure.
• Pregnant or breastfeeding individuals
• History of kidney disease
• History of insulin requiring diabetes
• Estimated glomerular filtration rate less than 60ml/min/1.73 m2, albumin creatinine ratio more than or equal to 30 mg/g
• Hepatic transaminase levels more than 3 times the upper limit of normal
• Anemia (men, Hb less than 13 g/dL; women, Hb less than 12 g/dL)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Hypertension; Genetic Risk Score

Interventions

Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nehal Vekariya, MS

CONTACT

2059347173; nvekariya@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Cardiovascular, Department of Medicine

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 12, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (1)