NAUTICAL: Effect of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals

NCT04055428 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 300003702R01HL163852
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Black individuals are more likely to have decreased insulin sensitivity which results in a high risk for the development of cardiometabolic disease. The reasons for this are incompletely understood. Natriuretic peptides (NPs) are hormones produced by the heart that play a role in regulating the metabolic health of an individual. Low circulating level of NPs is an important contributor to increased risk for diabetes. The NP levels are relatively lower among Black individuals thus affecting their metabolic health and putting them at a higher risk for diabetes. This study aims to test the hypothesis that by augmenting NP levels using sacubitril/valsartan, among Black Individuals one can improve their metabolic health (as measured by insulin sensitivity \& energy expenditure) and help establish the role of NPs in the underlying mechanism behind increased risk for cardiometabolic disease in these population.

Conditions

Diabetes Mellitus; Cardiovascular Diseases; Metabolic Disease; Natriuretic Peptides; Metabolism; Energy Expenditure; Insulin Sensitivity/Resistance

Keywords

Natriuretic Peptides; Diabetes; Insulin Sensitivity; Energy Expenditure

Outcome Measures

Primary Outcomes (2)

• Change in insulin sensitivity after natriuretic peptide augmentation

  An assessment of the insulin sensitivity will be done at baseline and after 12 weeks of pharmacological intervention.

  12 weeks

• Change in energy expenditure after natriuretic peptide augmentation

  An assessment of the resting energy expenditure will be done at baseline and after 12 weeks of pharmacological intervention.

  12 weeks

Secondary Outcomes (25)

• Change in exercise energy expenditure after 12 weeks of pharmacological intervention.

  12 weeks

• Change in post-meal increase in GLP-1 levels

  12 weeks

• Change in peak oxygen consumption after 12 weeks of pharmacological intervention.

  12 weeks

• Change in fasting GLP-1 levels

  12 weeks

• Change in natriuretic peptide levels

  12 weeks

Other Outcomes (1)

• Change in Metabolomic Profile

  12 weeks

Study Arms (2)

Sacubitril/Valsartan

EXPERIMENTAL

We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.

Drug: Sacubitril, Valsartan 97-103 mg Oral Tablet; Other: Intravenous Glucose Tolerance Test; Dietary Supplement: Standardized Meals; Other: Exercise capacity VO2 maximum determination

Valsartan

ACTIVE COMPARATOR

We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.

Drug: Valsartan 160 mg; Other: Intravenous Glucose Tolerance Test; Dietary Supplement: Standardized Meals; Other: Exercise capacity VO2 maximum determination

Interventions

Sacubitril, Valsartan 97-103 mg Oral Tablet DRUG

The subject will be randomized, in a double-blind manner to sacubitril/valsartan 97/103 mg twice daily for a period of 12 weeks.

Also known as: Sacubitril/Valsartan arm

Sacubitril/Valsartan

Valsartan 160 mg DRUG

The subject will be randomized, in a double-blind manner to valsartan 160 mg twice daily for a period of 12 weeks.

Also known as: Valsartan arm

Valsartan

Intravenous Glucose Tolerance Test OTHER

An assessment of the insulin sensitivity will be done using the IVGTT, at baseline and after 12 weeks of pharmacological interventions.

Sacubitril/Valsartan; Valsartan

Standardized Meals DIETARY_SUPPLEMENT

Participants will consume the standardized study mixed meal for the assessment of postprandial GLP-1 response to the meal.

Sacubitril/Valsartan; Valsartan

Exercise capacity VO2 maximum determination OTHER

Each participant's maximal oxygen capacity will be determined using modified Bruce treadmill protocol.

Sacubitril/Valsartan; Valsartan

Eligibility Criteria

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

You may qualify if:

• Adults: Age more than or equal to 18 years of age
• Self-identified race/ethnicity as African-American or Black
• Blood pressure: 120-160/80-100 mmHg

You may not qualify if:

• 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)
• Have any past or present history of cardiovascular diseases (stroke, myocardial infarction, heart failure, transient ischemic attack, angina, or cardiac arrhythmia)
• BP more than 160/100 mmHg
• BMI \>45 kg/m2
• History of diabetes or fasting plasma glucose \>=126 mg/dL or HbA1C\>=6.5%
• History of angioedema
• Current or past (\<12 months) history of smoking
• Estimated GFR \< 60 ml/min/1.73 m2; albumin-creatinine ratio ≥30 mg/g
• Hepatic Transaminase (AST and ALT) levels \>3x the upper limit of normal
• Significant psychiatric illness or seizure disorder
• More than 2 Alcoholic drinks daily
• Anemia (men, Hct \< 38%, Hb\<13 g/dL; women, Hct \<36%, Hb \<12 g/dL)
• Inability to exercise on a treadmill

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 (4)

• Jordan J, Stinkens R, Jax T, Engeli S, Blaak EE, May M, Havekes B, Schindler C, Albrecht D, Pal P, Heise T, Goossens GH, Langenickel TH. Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension. Clin Pharmacol Ther. 2017 Feb;101(2):254-263. doi: 10.1002/cpt.455. Epub 2016 Nov 17.

  PMID: 27542885 RESULT

• 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 RESULT

• Seferovic JP, Claggett B, Seidelmann SB, Seely EW, Packer M, Zile MR, Rouleau JL, Swedberg K, Lefkowitz M, Shi VC, Desai AS, McMurray JJV, Solomon SD. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 2017 May;5(5):333-340. doi: 10.1016/S2213-8587(17)30087-6. Epub 2017 Mar 18.

  PMID: 28330649 RESULT

• Patel N, Cushman M, Gutierrez OM, Howard G, Safford MM, Muntner P, Durant RW, Prabhu SD, Arora G, Levitan EB, Arora P. Racial differences in the association of NT-proBNP with risk of incident heart failure in REGARDS. JCI Insight. 2019 Jun 4;5(13):e129979. doi: 10.1172/jci.insight.129979.

  PMID: 31162140 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Cardiovascular Diseases; Insulin Resistance; Metabolic Diseases

Interventions

sacubitril; Valsartan; Tablets; Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

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; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

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

Study Design

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

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 13, 2019
• Study Start: August 15, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (1)