[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT04055428":3,"trial-entities:NCT04055428":213,"trial-summary:NCT04055428":217},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":26,"study_type":29,"primary_purpose":30,"phases":31,"enrollment_info":33,"interventions":36,"primary_outcomes":65,"secondary_outcomes":73,"sex":149,"minimum_age":150,"maximum_age":151,"healthy_volunteers":15,"eligibility_criteria":152,"std_ages":172,"locations":175,"central_contacts":193,"overall_officials":195,"references":198,"see_also_links":212},"NCT04055428","300003702","NAUTICAL: Effect of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals","The Effects of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals (NAUTICAL)","RECRUITING","2027-05-31","2026-07","2026-07-28","2020-08-15","University of Alabama at Birmingham","OTHER",true,"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\u002Fvalsartan, 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.","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.\n\nEvidence 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.\n\nSacubitril\u002Fvalsartan is an FDA-approved inhibitor of neprilysin that augment NP levels. NP augmentation using sacubitril\u002Fvalsartan 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.\n\nWe 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\u002Fvalsartan versus valsartan alone.\n\nOur study will have the following aims. The first aim is to assess the change in the insulin sensitivity after NP augmentation therapy (using sacubitril\u002Fvalsartan) 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.\n\nThe second aim of our study is to examine the change in the energy expenditure after sacubitril\u002Fvalsartan 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\u002Fvalsartan or valsartan alone.\n\nThe secondary aim of our study is to assess the GLP-1 response to meals after treatment with sacubitril\u002Fvalsartan in Black individuals. We will evaluate the change in postprandial GLP-1 response to meals at baseline and after 12 weeks of either sacubitril\u002Fvalsartan or valsartan alone.",[19,20,21,22,23,24,25],"Diabetes Mellitus","Cardiovascular Diseases","Insulin Sensitivity\u002FResistance","Metabolic Disease","Natriuretic Peptides","Metabolism","Energy Expenditure",[23,27,28,25],"Diabetes","Insulin Sensitivity","INTERVENTIONAL","TREATMENT",[32],"PHASE2",{"count":34,"type":35},200,"ESTIMATED",[37,45,52,56,61],{"type":38,"name":39,"description":40,"armGroupLabels":41,"otherNames":43},"DRUG","Sacubitril, Valsartan 97-103 mg Oral Tablet","The subject will be randomized, in a double-blind manner to sacubitril\u002Fvalsartan 97\u002F103 mg twice daily for a period of 12 weeks.",[42],"Sacubitril\u002FValsartan",[44],"Sacubitril\u002FValsartan arm",{"type":38,"name":46,"description":47,"armGroupLabels":48,"otherNames":50},"Valsartan 160 mg","The subject will be randomized, in a double-blind manner to valsartan 160 mg twice daily for a period of 12 weeks.",[49],"Valsartan",[51],"Valsartan arm",{"type":14,"name":53,"description":54,"armGroupLabels":55},"Intravenous Glucose Tolerance Test","An assessment of the insulin sensitivity will be done using the IVGTT, at baseline and after 12 weeks of pharmacological interventions.",[42,49],{"type":57,"name":58,"description":59,"armGroupLabels":60},"DIETARY_SUPPLEMENT","Standardized Meals","Participants will consume the standardized study mixed meal for the assessment of postprandial GLP-1 response to the meal.",[42,49],{"type":14,"name":62,"description":63,"armGroupLabels":64},"Exercise capacity VO2 maximum determination","Each participant's maximal oxygen capacity will be determined using modified Bruce treadmill protocol.",[42,49],[66,70],{"measure":67,"description":68,"timeFrame":69},"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",{"measure":71,"description":72,"timeFrame":69},"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.",[74,77,80,83,86,89,92,95,98,101,104,107,110,113,116,119,122,125,128,131,134,137,140,143,146],{"measure":75,"description":76,"timeFrame":69},"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.",{"measure":78,"description":79,"timeFrame":69},"Change in post-meal increase in GLP-1 levels","Change in GLP-1 levels after a standardized meal after 12 weeks of pharmacological intervention",{"measure":81,"description":82,"timeFrame":69},"Change in peak oxygen consumption after 12 weeks of pharmacological intervention.","Change in the peak oxygen consumption (VO2 max) after 12 weeks of intervention.",{"measure":84,"description":85,"timeFrame":69},"Change in fasting GLP-1 levels","Change in fasting GLP-1 levels after 12 weeks of pharmacological intervention",{"measure":87,"description":88,"timeFrame":69},"Change in natriuretic peptide levels","Change in natriuretic peptide levels (ANP, MRproANP, BNP, NTproBNP) after 12 weeks of pharmacological intervention",{"measure":90,"description":91,"timeFrame":69},"Change in measures of insulin sensitivity","Change in measures of insulin sensitivity (AIRg, Sg, Kg, Disposition Index) after 12 weeks of pharmacological intervention",{"measure":93,"description":94,"timeFrame":69},"Change in HBA1c levels","Change in HBA1c levels after 12 weeks of pharmacological intervention",{"measure":96,"description":97,"timeFrame":69},"Change in fasting blood glucose levels","Change in fasting blood glucose levels after 12 weeks of pharmacological intervention",{"measure":99,"description":100,"timeFrame":69},"Change in HOMA-IR","Change in HOMA-IR after 12 weeks of pharmacological intervention",{"measure":102,"description":103,"timeFrame":69},"Change in fasting insulin levels","Change in fasting insulin levels after 12 weeks of pharmacological intervention",{"measure":105,"description":106,"timeFrame":69},"Change in measures of body mass index","Change in the measures of body mass index after 12 weeks of pharmacological intervention",{"measure":108,"description":109,"timeFrame":69},"Change in measures of hip circumference","Change in the measures of hip circumference after 12 weeks of pharmacological intervention",{"measure":111,"description":112,"timeFrame":69},"Change in measures of waist circumference","Change in the measures of waist circumference after 12 weeks of pharmacological intervention",{"measure":114,"description":115,"timeFrame":69},"Change in measures of adipose tissue mass","Change in the measures of adipose tissue mass after 12 weeks of pharmacological intervention",{"measure":117,"description":118,"timeFrame":69},"Change in total cholesterol levels","Change in the total cholesterol levels after 12 weeks of pharmacological intervention",{"measure":120,"description":121,"timeFrame":69},"Change in LDL-C levels","Change in LDL-C levels after 12 weeks of pharmacological intervention",{"measure":123,"description":124,"timeFrame":69},"Change in HDL-C levels","Change in HDL-C levels after 12 weeks of pharmacological intervention",{"measure":126,"description":127,"timeFrame":69},"Change in triglyceride levels","Change in triglyceride levels after 12 weeks of pharmacological intervention",{"measure":129,"description":130,"timeFrame":69},"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.",{"measure":132,"description":133,"timeFrame":69},"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.",{"measure":135,"description":136,"timeFrame":69},"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.",{"measure":138,"description":139,"timeFrame":69},"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.",{"measure":141,"description":142,"timeFrame":69},"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.",{"measure":144,"description":145,"timeFrame":69},"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.",{"measure":147,"description":148,"timeFrame":69},"Impact of Natriuretic Peptide Genotype on Study Endpoints","All study outcomes will be analyzed by natriuretic peptide genotypes","ALL","18 Years",null,{"inclusion":153,"exclusion":157,"raw_text":171},[154,155,156],"Adults: Age more than or equal to 18 years of age","Self-identified race\u002Fethnicity as African-American or Black","Blood pressure: 120-160\u002F80-100 mmHg",[158,159,160,161,162,163,164,165,166,167,168,169,170],"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\u002F100 mmHg","BMI \\>45 kg\u002Fm2","History of diabetes or fasting plasma glucose \\>=126 mg\u002FdL or HbA1C\\>=6.5%","History of angioedema","Current or past (\\\u003C12 months) history of smoking","Estimated GFR \\\u003C 60 ml\u002Fmin\u002F1.73 m2; albumin-creatinine ratio ≥30 mg\u002Fg","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 \\\u003C 38%, Hb\\\u003C13 g\u002FdL; women, Hct \\\u003C36%, Hb \\\u003C12 g\u002FdL)","Inability to exercise on a treadmill","Inclusion Criteria:\n\n* Adults: Age more than or equal to 18 years of age\n* Self-identified race\u002Fethnicity as African-American or Black\n* Blood pressure: 120-160\u002F80-100 mmHg\n\nExclusion Criteria:\n\n* 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)\n* Have any past or present history of cardiovascular diseases (stroke, myocardial infarction, heart failure, transient ischemic attack, angina, or cardiac arrhythmia)\n* BP more than 160\u002F100 mmHg\n* BMI \\>45 kg\u002Fm2\n* History of diabetes or fasting plasma glucose \\>=126 mg\u002FdL or HbA1C\\>=6.5%\n* History of angioedema\n* Current or past (\\\u003C12 months) history of smoking\n* Estimated GFR \\\u003C 60 ml\u002Fmin\u002F1.73 m2; albumin-creatinine ratio ≥30 mg\u002Fg\n* Hepatic Transaminase (AST and ALT) levels \\>3x the upper limit of normal\n* Significant psychiatric illness or seizure disorder\n* More than 2 Alcoholic drinks daily\n* Anemia (men, Hct \\\u003C 38%, Hb\\\u003C13 g\u002FdL; women, Hct \\\u003C36%, Hb \\\u003C12 g\u002FdL)\n* Inability to exercise on a treadmill",[173,174],"ADULT","OLDER_ADULT",[176],{"facility":13,"status":8,"city":177,"state":178,"zip":179,"country":180,"contacts":181,"geoPoint":190},"Birmingham","Alabama","35294","United States",[182,187],{"name":183,"role":184,"phone":185,"email":186},"Nehal Vekariya, MS","CONTACT","205-934-7173","nvekariya@uabmc.edu",{"name":188,"role":189},"Pankaj Arora, MD","PRINCIPAL_INVESTIGATOR",{"lat":191,"lon":192},33.52066,-86.80249,[194],{"name":183,"role":184,"phone":185,"email":186},[196],{"name":197,"affiliation":13,"role":189},"Pankaj Arora, MD, FAHA",[199,203,206,209],{"pmid":200,"type":201,"citation":202},"27542885","RESULT","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\u002Fcpt.455. Epub 2016 Nov 17.",{"pmid":204,"type":201,"citation":205},"25595796","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\u002FJAHA.114.001265.",{"pmid":207,"type":201,"citation":208},"28330649","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\u002Fvalsartan 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\u002FS2213-8587(17)30087-6. Epub 2017 Mar 18.",{"pmid":210,"type":201,"citation":211},"31162140","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\u002Fjci.insight.129979.",[],{"nct_id":4,"conditions":214,"biomarkers":216},[215,19],"Cardiovascular Disorder",[],{"nct_id":4,"found":15,"summary":218,"prompt_version":228},{"design":219,"status":220,"heading":221,"summary":222,"follow_up":223,"word_count":224,"commitments":225,"compensation":226,"drugs_mentioned":227},"This is an interventional study planning to enroll 200 participants. You would be randomly assigned, without you or the researchers knowing, to receive either sacubitril\u002Fvalsartan or valsartan.","completed","NAUTICAL: Sacubitril\u002FValsartan for Cardiometabolic Health in Black Individuals","This study, called NAUTICAL, is looking at how a medication called sacubitril\u002Fvalsartan (Entresto) might improve heart and metabolism health in Black individuals. Black individuals often have lower levels of natural hormones called natriuretic peptides (NPs), which are important for how your body uses insulin and energy. Researchers believe that increasing these NP levels with sacubitril\u002Fvalsartan could help improve insulin sensitivity (how well your body responds to insulin) and overall metabolic health. You might be able to join if you are an adult (18 or older) who identifies as African-American or Black and have blood pressure between 120-160\u002F80-100 mmHg. The study will measure changes in your insulin sensitivity and how your body uses energy after 12 weeks of treatment. The current status of this study is unclear.","Your insulin sensitivity and energy expenditure will be measured at 12 weeks after starting the interventions.",126,"You would take either sacubitril\u002Fvalsartan or valsartan twice daily for 12 weeks. You would also have an intravenous glucose tolerance test (IVGTT) at the beginning and end of the 12 weeks, eat standardized meals, and have your exercise capacity measured.","Not stated in the trial record.",[],"v2"]