Diabetes MellitusPhase 2NCT04055428
NAUTICAL: Effect of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals
A Phase 2 study testing Sacubitril, Valsartan 97-103 mg Oral Tablet, Valsartan 160 mg and Intravenous Glucose Tolerance Test in people with Diabetes Mellitus and Cardiovascular Diseases, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Cardiovascular Diseases, Insulin Sensitivity/Resistance
- What is being tested?
- Sacubitril, Valsartan 97-103 mg Oral Tablet, Valsartan 160 mg and Intravenous Glucose Tolerance Test
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2020to 31 May 2027
- Phase
- Phase 2
- 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
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Nehal Vekariya, MS, 205-934-7173, nvekariya@uabmc.edu
Pankaj Arora, MD
About this study
Official title: The Effects of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals (NAUTICAL)
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.
Read the detailed description
Black individuals are more likely to have a reduced insulin sensitivity which results in a greater risk for diabetes. However, the reasons for their decreased insulin sensitivity are not clearly understood. Natriuretic peptides (NPs) are hormones produced by the heart that is known to have a wide range of favorable metabolic effects. Studies indicate that lower NP levels are associated with a decreased insulin sensitivity and this may be causally related to the development of diabetes.
Evidence suggests that Black individuals have low levels of NPs. Increased clearance of NPs by neprilysin, an NP degrading enzyme, contributes to the low levels of NP among Black individuals. Since NPs play an important role in the regulation of insulin sensitivity and energy expenditure, one can infer that relatively low NP levels are an important biological contributor to the high prevalence rates of cardiometabolic disease in African Americans.
Sacubitril/valsartan is an FDA-approved inhibitor of neprilysin that augment NP levels. NP augmentation using sacubitril/valsartan has been shown to improve insulin sensitivity and lipid metabolism in a small clinical trial among obese White individuals. It can be postulated that NP augmentation in populations with relatively low NP levels will help in improving their metabolic health. Improvement in the metabolic health following NP augmentation will also help us to outline the relationship between the NP system and the risk of cardiometabolic disease among Black individuals.
We hypothesize that NP augmentation among Black individuals will show an improvement in their metabolic health as measured by insulin sensitivity and energy expenditure. We hypothesize that African American individuals will show an improvement in their insulin sensitivity and their resting \& exercise energy expenditure after treatment with sacubitril/valsartan versus valsartan alone.
Our study will have the following aims. The first aim is to assess the change in the insulin sensitivity after NP augmentation therapy (using sacubitril/valsartan) as compared with NP neutral therapy (using valsartan) among Black individuals. We will measure the change in insulin sensitivity (assessed using IVGTT) after 12 weeks of intervention. We will also assess the change in NP levels (a marker of NP augmentation) \& cyclic guanylate monophosphate (cGMP) levels after intervention and evaluate their relationship with the change in insulin sensitivity.
The second aim of our study is to examine the change in the energy expenditure after sacubitril/valsartan as compared to valsartan alone among Black individuals. The individuals enrolled in the first aim will also be examined for the change in resting as well as exercise energy expenditure. This will be assessed using standardized protocol performed using the metabolic cart and an exercise treadmill, at baseline and after 12 weeks of either sacubitril/valsartan or valsartan alone.
The secondary aim of our study is to assess the GLP-1 response to meals after treatment with sacubitril/valsartan in Black individuals. We will evaluate the change in postprandial GLP-1 response to meals at baseline and after 12 weeks of either sacubitril/valsartan or valsartan alone.
- Conditions
- Diabetes Mellitus, Cardiovascular Diseases, Insulin Sensitivity/Resistance, Metabolic Disease, Natriuretic Peptides, Metabolism
- Being tested
- Sacubitril, Valsartan 97-103 mg Oral Tablet, Valsartan 160 mg, Intravenous Glucose Tolerance Test, Standardized Meals, Exercise capacity VO2 maximum determination
- Keywords
- Natriuretic Peptides, Diabetes, Insulin Sensitivity, Energy Expenditure
- Medical subject headings
- Diabetes Mellitus, Cardiovascular Diseases, Insulin Resistance, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril, Valsartan 97-103 mg Oral TabletDrug
Also called Sacubitril/Valsartan arm
The subject will be randomized, in a double-blind manner to sacubitril/valsartan 97/103 mg twice daily for a period of 12 weeks.
Valsartan 160 mgDrug
Also called Valsartan arm
The subject will be randomized, in a double-blind manner to valsartan 160 mg twice daily for a period of 12 weeks.
Intravenous Glucose Tolerance TestOther
An assessment of the insulin sensitivity will be done using the IVGTT, at baseline and after 12 weeks of pharmacological interventions.
Standardized MealsDietary supplement
Participants will consume the standardized study mixed meal for the assessment of postprandial GLP-1 response to the meal.
Exercise capacity VO2 maximum determinationOther
Each participant's maximal oxygen capacity will be determined using modified Bruce treadmill protocol.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Valsartan 160 mg; Other: Intravenous Glucose Tolerance Test; Dietary Supplement: Standardized Meals; Other: Exercise capacity VO2 maximum determination |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks
Secondary outcomes (25)
Change in exercise energy expenditure after 12 weeks of pharmacological intervention.
During standardized protocol after 12 weeks of intervention, the energy expenditure will be calculated using metabolic cart.
Measured: 12 weeks
Change in post-meal increase in GLP-1 levels
Change in GLP-1 levels after a standardized meal after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in peak oxygen consumption after 12 weeks of pharmacological intervention.
Change in the peak oxygen consumption (VO2 max) after 12 weeks of intervention.
Measured: 12 weeks
Change in fasting GLP-1 levels
Change in fasting GLP-1 levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in natriuretic peptide levels
Change in natriuretic peptide levels (ANP, MRproANP, BNP, NTproBNP) after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in measures of insulin sensitivity
Change in measures of insulin sensitivity (AIRg, Sg, Kg, Disposition Index) after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in HBA1c levels
Change in HBA1c levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in fasting blood glucose levels
Change in fasting blood glucose levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in HOMA-IR
Change in HOMA-IR after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in fasting insulin levels
Change in fasting insulin levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in measures of body mass index
Change in the measures of body mass index after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in measures of hip circumference
Change in the measures of hip circumference after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in measures of waist circumference
Change in the measures of waist circumference after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in measures of adipose tissue mass
Change in the measures of adipose tissue mass after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in total cholesterol levels
Change in the total cholesterol levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in LDL-C levels
Change in LDL-C levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in HDL-C levels
Change in HDL-C levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Change in triglyceride levels
Change in triglyceride levels after 12 weeks of pharmacological intervention
Measured: 12 weeks
Correlation of change in MR-pro atrial natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in MR-pro atrial natriuretic peptide levels with change in insulin sensitivity after 12 weeks of intervention will be examined.
Measured: 12 weeks
Correlation of change in MR-pro atrial natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in MR-pro atrial natriuretic peptide levels with change in resting and exercise energy expenditure after 12 weeks of intervention will be examined.
Measured: 12 weeks
Correlation of change in B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of intervention will be examined.
Measured: 12 weeks
Correlation of change in B-type natriuretic peptide levels with change in resting energy expenditure after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in B-type natriuretic peptide levels with change in resting energy expenditure after 12 weeks of intervention will be examined.
Measured: 12 weeks
Correlation of change in NT-pro B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in NT-pro B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of intervention will be examined.
Measured: 12 weeks
Correlation of change in NT-pro B-type natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.
The exposure-response relationship of change in NT-pro B-type natriuretic peptide levels with change in resting and exercise energy expenditure after 12 weeks of intervention will be examined.
Measured: 12 weeks
Impact of Natriuretic Peptide Genotype on Study Endpoints
All study outcomes will be analyzed by natriuretic peptide genotypes
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2019
- Study start15 Aug 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Pankaj Arora, MD, University of Alabama at Birmingham
- Investigators
- Pankaj Arora, MD, FAHA, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04055428
- Sponsor's protocol ID
- 300003702
- Other IDs
- R01HL163852
- Status last verified
- Jul 2026
- First submitted
- 7 Aug 2019
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27542885Arora 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 25595796Seferovic 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.
PubMed 28330649Patel 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.
PubMed 31162140
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals (NAUTICAL)
- ClinicalTrials.gov ID
- NCT04055428
- Acronym / sponsor ID
- 300003702
- Conditions
- Diabetes Mellitus, Cardiovascular Diseases, Insulin Sensitivity/Resistance, Metabolic Disease, Natriuretic Peptides, Metabolism
- Keywords
- Natriuretic Peptides, Diabetes, Insulin Sensitivity, Energy Expenditure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 15 Aug 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 13 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Black individuals are more likely to have a reduced insulin sensitivity which results in a greater risk for diabetes. However, the reasons for their decreased insulin sensitivity are not clearly understood. Natriuretic peptides (NPs) are hormones produced by the heart that is known to have a wide range of favorable metabolic effects. Studies indicate that lower NP levels are associated with a decreased insulin sensitivity and this may be causally related to the development of diabetes.
Evidence suggests that Black individuals have low levels of NPs. Increased clearance of NPs by neprilysin, an NP degrading enzyme, contributes to the low levels of NP among Black individuals. Since NPs play an important role in the regulation of insulin sensitivity and energy expenditure, one can infer that relatively low NP levels are an important biological contributor to the high prevalence rates of cardiometabolic disease in African Americans.
Sacubitril/valsartan is an FDA-approved inhibitor of neprilysin that augment NP levels. NP augmentation using sacubitril/valsartan has been shown to improve insulin sensitivity and lipid metabolism in a small clinical trial among obese White individuals. It can be postulated that NP augmentation in populations with relatively low NP levels will help in improving their metabolic health. Improvement in the metabolic health following NP augmentation will also help us to outline the relationship between the NP system and the risk of cardiometabolic disease among Black individuals.
We hypothesize that NP augmentation among Black individuals will show an improvement in their metabolic health as measured by insulin sensitivity and energy expenditure. We hypothesize that African American individuals will show an improvement in their insulin sensitivity and their resting \& exercise energy expenditure after treatment with sacubitril/valsartan versus valsartan alone.
Our study will have the following aims. The first aim is to assess the change in the insulin sensitivity after NP augmentation therapy (using sacubitril/valsartan) as compared with NP neutral therapy (using valsartan) among Black individuals. We will measure the change in insulin sensitivity (assessed using IVGTT) after 12 weeks of intervention. We will also assess the change in NP levels (a marker of NP augmentation) \& cyclic guanylate monophosphate (cGMP) levels after intervention and evaluate their relationship with the change in insulin sensitivity.
The second aim of our study is to examine the change in the energy expenditure after sacubitril/valsartan as compared to valsartan alone among Black individuals. The individuals enrolled in the first aim will also be examined for the change in resting as well as exercise energy expenditure. This will be assessed using standardized protocol performed using the metabolic cart and an exercise treadmill, at baseline and after 12 weeks of either sacubitril/valsartan or valsartan alone.
The secondary aim of our study is to assess the GLP-1 response to meals after treatment with sacubitril/valsartan in Black individuals. We will evaluate the change in postprandial GLP-1 response to meals at baseline and after 12 weeks of either sacubitril/valsartan or valsartan alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril/Valsartan | Experimental | Drug: Sacubitril, Valsartan 97-103 mg Oral Tablet, Other: Intravenous Glucose Tolerance Test, Dietary Supplement: Standardized Meals, Other: Exercise capacity VO2 maximum determinationWe 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. |
| Valsartan | Active comparator | Drug: Valsartan 160 mg, Other: Intravenous Glucose Tolerance Test, Dietary Supplement: Standardized Meals, Other: Exercise capacity VO2 maximum determinationWe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril, Valsartan 97-103 mg Oral TabletAlso: Sacubitril/Valsartan armThe subject will be randomized, in a double-blind manner to sacubitril/valsartan 97/103 mg twice daily for a period of 12 weeks. | Drug | Sacubitril/Valsartan |
| Valsartan 160 mgAlso: Valsartan armThe subject will be randomized, in a double-blind manner to valsartan 160 mg twice daily for a period of 12 weeks. | Drug | Valsartan |
| Intravenous Glucose Tolerance TestAn assessment of the insulin sensitivity will be done using the IVGTT, at baseline and after 12 weeks of pharmacological interventions. | Other | Sacubitril/Valsartan, Valsartan |
| Standardized MealsParticipants will consume the standardized study mixed meal for the assessment of postprandial GLP-1 response to the meal. | Dietary supplement | Sacubitril/Valsartan, Valsartan |
| Exercise capacity VO2 maximum determinationEach participant's maximal oxygen capacity will be determined using modified Bruce treadmill protocol. | Other | Sacubitril/Valsartan, Valsartan |
Primary outcome
Change in insulin sensitivity after natriuretic peptide augmentation
Time frame: 12 weeks
An assessment of the insulin sensitivity will be done at baseline and after 12 weeks of pharmacological intervention.
Change in energy expenditure after natriuretic peptide augmentation
Time frame: 12 weeks
An assessment of the resting energy expenditure will be done at baseline and after 12 weeks of pharmacological intervention.
25 secondary outcomes
Change in exercise energy expenditure after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Change in post-meal increase in GLP-1 levels
Time frame: 12 weeks
Change in peak oxygen consumption after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Change in fasting GLP-1 levels
Time frame: 12 weeks
Change in natriuretic peptide levels
Time frame: 12 weeks
Change in measures of insulin sensitivity
Time frame: 12 weeks
Change in HBA1c levels
Time frame: 12 weeks
Change in fasting blood glucose levels
Time frame: 12 weeks
Change in HOMA-IR
Time frame: 12 weeks
Change in fasting insulin levels
Time frame: 12 weeks
Change in measures of body mass index
Time frame: 12 weeks
Change in measures of hip circumference
Time frame: 12 weeks
Change in measures of waist circumference
Time frame: 12 weeks
Change in measures of adipose tissue mass
Time frame: 12 weeks
Change in total cholesterol levels
Time frame: 12 weeks
Change in LDL-C levels
Time frame: 12 weeks
Change in HDL-C levels
Time frame: 12 weeks
Change in triglyceride levels
Time frame: 12 weeks
Correlation of change in MR-pro atrial natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Correlation of change in MR-pro atrial natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Correlation of change in B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Correlation of change in B-type natriuretic peptide levels with change in resting energy expenditure after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Correlation of change in NT-pro B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Correlation of change in NT-pro B-type natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.
Time frame: 12 weeks
Impact of Natriuretic Peptide Genotype on Study Endpoints
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Results publication: PubMed 27542885Jordan 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.
- Results publication: PubMed 25595796Arora 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.
- Results publication: PubMed 28330649Seferovic 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.
- Results publication: PubMed 31162140Patel 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pankaj Arora, MD, FAHA principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacubitril, Valsartan 97-103 mg Oral Tablet, Valsartan 160 mg and Intravenous Glucose Tolerance Test in people with Diabetes Mellitus 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 28 Jul 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 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.
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 insulin sensitivity after natriuretic peptide augmentation (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT04055428, which also lists 4 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 28 Jul 2026.