Ignite Creation Date:
2025-12-24 @ 11:52 PM
Ignite Modification Date:
2026-01-01 @ 9:06 AM
Study NCT ID:
NCT03234751
Status:
COMPLETED
Last Update Posted:
2020-03-10
First Post:
2017-07-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}], 'ancestors': [{'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'This study is prospective randomized, double masked, 2-period cross over design, proof of concept study of the effects of intravenously administered rhBNP (nesiritide) on insulin sensitivity in otherwise healthy obese nondiabetic insulin resistant subjects.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 6}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-07-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2020-02-19', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-09', 'studyFirstSubmitDate': '2017-07-18', 'studyFirstSubmitQcDate': '2017-07-26', 'lastUpdatePostDateStruct': {'date': '2020-03-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-07-31', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-09-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'IV infusion of nesiritide at a 3pmol/kg rate', 'timeFrame': '48 hours', 'description': 'Average changes in glucose disposal rates (GDR) and endogenous glucose production (EGP) from baseline corrected for body weight at steady state of the clamp during the high- and low-dose portions.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['human B-type natriuretic peptide'], 'conditions': ['Diabetes']}, 'referencesModule': {'references': [{'pmid': '18636063', 'type': 'BACKGROUND', 'citation': 'Centers for Disease Control and Prevention (CDC). State-specific prevalence of obesity among adults--United States, 2007. MMWR Morb Mortal Wkly Rep. 2008 Jul 18;57(28):765-8.'}, {'pmid': '16380542', 'type': 'BACKGROUND', 'citation': 'Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH; American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006 Feb 14;113(6):898-918. doi: 10.1161/CIRCULATIONAHA.106.171016. Epub 2005 Dec 27.'}, {'pmid': '15181019', 'type': 'BACKGROUND', 'citation': 'Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.'}, {'pmid': '14749502', 'type': 'BACKGROUND', 'citation': 'Aneja A, El-Atat F, McFarlane SI, Sowers JR. Hypertension and obesity. Recent Prog Horm Res. 2004;59:169-205. doi: 10.1210/rp.59.1.169.'}, {'pmid': '17414649', 'type': 'BACKGROUND', 'citation': 'Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S, Reid J, Van Zwieten PA. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007 May;25(5):909-20. doi: 10.1097/HJH.0b013e328048d004.'}, {'pmid': '10440591', 'type': 'BACKGROUND', 'citation': 'Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res. 1999 Jul;7(4):355-62. doi: 10.1002/j.1550-8528.1999.tb00418.x.'}, {'pmid': '8957740', 'type': 'BACKGROUND', 'citation': 'Sarzani R, Dessi-Fulgheri P, Paci VM, Espinosa E, Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues. J Endocrinol Invest. 1996 Oct;19(9):581-5. doi: 10.1007/BF03349021.'}, {'pmid': '14769680', 'type': 'BACKGROUND', 'citation': 'Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004 Feb 10;109(5):594-600. doi: 10.1161/01.CIR.0000112582.16683.EA.'}, {'pmid': '16291870', 'type': 'BACKGROUND', 'citation': 'Potter LR, Abbey-Hosch S, Dickey DM. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev. 2006 Feb;27(1):47-72. doi: 10.1210/er.2005-0014. Epub 2005 Nov 16.'}, {'pmid': '21849523', 'type': 'BACKGROUND', 'citation': 'Khan AM, Cheng S, Magnusson M, Larson MG, Newton-Cheh C, McCabe EL, Coviello AD, Florez JC, Fox CS, Levy D, Robins SJ, Arora P, Bhasin S, Lam CS, Vasan RS, Melander O, Wang TJ. Cardiac natriuretic peptides, obesity, and insulin resistance: evidence from two community-based studies. J Clin Endocrinol Metab. 2011 Oct;96(10):3242-9. doi: 10.1210/jc.2011-1182. Epub 2011 Aug 17.'}, {'pmid': '21059435', 'type': 'BACKGROUND', 'citation': 'Chen-Tournoux A, Khan AM, Baggish AL, Castro VM, Semigran MJ, McCabe EL, Moukarbel G, Reingold J, Durrani S, Lewis GD, Newton-Cheh C, Scherrer-Crosbie M, Kaplan LM, Wang TJ. Effect of weight loss after weight loss surgery on plasma N-terminal pro-B-type natriuretic peptide levels. Am J Cardiol. 2010 Nov 15;106(10):1450-5. doi: 10.1016/j.amjcard.2010.06.076.'}, {'pmid': '21959345', 'type': 'BACKGROUND', 'citation': 'Bertoni AG, Wagenknecht LE, Kitzman DW, Marcovina SM, Rushing JT, Espeland MA; Brain Natriuretic Peptide Subgroup of the Look AHEAD Research Group. Impact of the look AHEAD intervention on NT-pro brain natriuretic peptide in overweight and obese adults with diabetes. Obesity (Silver Spring). 2012 Jul;20(7):1511-8. doi: 10.1038/oby.2011.296. Epub 2011 Sep 29.'}, {'pmid': '19477358', 'type': 'BACKGROUND', 'citation': 'Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M. Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol. 2009 Jun 2;53(22):2070-7. doi: 10.1016/j.jacc.2009.02.038.'}, {'pmid': '22419733', 'type': 'BACKGROUND', 'citation': 'Pivovarova O, Gogebakan O, Kloting N, Sparwasser A, Weickert MO, Haddad I, Nikiforova VJ, Bergmann A, Kruse M, Seltmann AC, Bluher M, Pfeiffer AF, Rudovich N. Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity? J Clin Endocrinol Metab. 2012 May;97(5):E731-9. doi: 10.1210/jc.2011-2839. Epub 2012 Mar 14.'}, {'pmid': '19690065', 'type': 'BACKGROUND', 'citation': 'Miyashita K, Itoh H, Tsujimoto H, Tamura N, Fukunaga Y, Sone M, Yamahara K, Taura D, Inuzuka M, Sonoyama T, Nakao K. Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity. Diabetes. 2009 Dec;58(12):2880-92. doi: 10.2337/db09-0393. Epub 2009 Aug 18.'}, {'pmid': '22159910', 'type': 'BACKGROUND', 'citation': 'Heinisch BB, Vila G, Resl M, Riedl M, Dieplinger B, Mueller T, Luger A, Pacini G, Clodi M. B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men. Diabetologia. 2012 May;55(5):1400-5. doi: 10.1007/s00125-011-2392-1. Epub 2011 Dec 13.'}, {'pmid': '22307324', 'type': 'BACKGROUND', 'citation': 'Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, Takahashi N, Sarzani R, Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012 Mar;122(3):1022-36. doi: 10.1172/JCI59701. Epub 2012 Feb 6.'}, {'pmid': '24595856', 'type': 'BACKGROUND', 'citation': 'Plante E, Menaouar A, Danalache BA, Broderick TL, Jankowski M, Gutkowska J. Treatment with brain natriuretic peptide prevents the development of cardiac dysfunction in obese diabetic db/db mice. Diabetologia. 2014 Jun;57(6):1257-67. doi: 10.1007/s00125-014-3201-4. Epub 2014 Mar 5.'}, {'pmid': '26543510', 'type': 'BACKGROUND', 'citation': 'Shankar SS, Shankar RR, Railkar RA, Beals CR, Steinberg HO, Kelley DE. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population. Curr Ther Res Clin Exp. 2015 Aug 14;77:83-9. doi: 10.1016/j.curtheres.2015.08.001. eCollection 2015 Dec.'}, {'pmid': '8380606', 'type': 'BACKGROUND', 'citation': 'Holmes SJ, Espiner EA, Richards AM, Yandle TG, Frampton C. Renal, endocrine, and hemodynamic effects of human brain natriuretic peptide in normal man. J Clin Endocrinol Metab. 1993 Jan;76(1):91-6. doi: 10.1210/jcem.76.1.8380606.'}, {'pmid': '22698919', 'type': 'BACKGROUND', 'citation': 'Vila G, Grimm G, Resl M, Heinisch B, Einwallner E, Esterbauer H, Dieplinger B, Mueller T, Luger A, Clodi M. B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men. Diabetes. 2012 Oct;61(10):2592-6. doi: 10.2337/db11-1466. Epub 2012 Jun 14.'}, {'pmid': '16755284', 'type': 'BACKGROUND', 'citation': 'Mojiminiyi OA, Abdella NA, Al Arouj M, Ben Nakhi A. Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes. Int J Obes (Lond). 2007 Feb;31(2):213-20. doi: 10.1038/sj.ijo.0803355. Epub 2006 Jun 6.'}, {'pmid': '25053801', 'type': 'BACKGROUND', 'citation': 'Timar R, Timar B, Degeratu D, Serafinceanu C, Oancea C. Metabolic syndrome, adiponectin and proinflammatory status in patients with type 1 diabetes mellitus. J Int Med Res. 2014 Oct;42(5):1131-8. doi: 10.1177/0300060514541829. Epub 2014 Jul 22.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of the study is to compare the effects of nesiritide to placebo administered by a continuous IV infusion over 48 hours for the treatment of insulin resistance in healthy, obese, insulin resistant individuals.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '40 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age 40-65 years inclusive\n2. Men and women\n3. Able to provide written, informed consent\n4. Weight stable (± 3 kg) during the 3 months prior to enrollment\n5. BMI ≥ 30 kg/m2; body weight ≤ 106 kg\n6. Resting blood pressure ≥ 110/60 mmHg and ≤ 150/100 mmHg\n\nExclusion Criteria:\n\n1. Known coronary artery disease, angina or heart failure\n2. Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose \\>125mg/dL)\n3. Bleeding disorders\n4. Hemoglobin level \\< 12.5 g/dL for women; \\< 13.0 g/dL for men\n5. Acute or chronic infections\n6. Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal)\n7. Severe asthma or chronic obstructive pulmonary disease\n8. Renal insufficiency (creatinine \\> 1.6 mg/dL)\n9. Prior bariatric surgery\n10. Inflammatory bowel disease or malabsorption\n11. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)\n12. Psychiatric or eating disorders\n13. Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders\n14. Active rheumatoid arthritis or other inflammatory rheumatic disorder\n15. Pregnant or nursing women\n16. Presence of clinically significant abnormalities on electrocardiogram\n17. Smoking (within the last 3 months)\n18. Known hypersensitivity to nesiritide or any of its excipients\n19. Poor intravenous access\n20. Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable), f) chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phenteramine or other weight loss or anorectic agents.'}, 'identificationModule': {'nctId': 'NCT03234751', 'acronym': 'BNP3', 'briefTitle': 'Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects', 'organization': {'class': 'OTHER', 'fullName': 'AdventHealth Translational Research Institute'}, 'officialTitle': 'Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects', 'orgStudyIdInfo': {'id': 'TRIMDFH 1081082'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Obese nondiabetic insulin resistant subjects- Panel A', 'description': 'IV nesiritide 3 pmol/kg/min or placebo for nesiritide', 'interventionNames': ['Drug: Continous IV infusion of Nesiritide', 'Drug: Hyperinsulinemic euglycemic clamp', 'Drug: Placebo']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Obese nondiabetic insulin resistant subjects- Panel B', 'description': 'IV nesiritide 2 pmol/kg/min or placebo for nesiritide', 'interventionNames': ['Drug: Continous IV infusion of Nesiritide', 'Drug: Hyperinsulinemic euglycemic clamp', 'Drug: Placebo']}], 'interventions': [{'name': 'Continous IV infusion of Nesiritide', 'type': 'DRUG', 'description': 'Nesiritide (fhBNP) administered by continuous IV infusion during 48 hours.', 'armGroupLabels': ['Obese nondiabetic insulin resistant subjects- Panel A', 'Obese nondiabetic insulin resistant subjects- Panel B']}, {'name': 'Hyperinsulinemic euglycemic clamp', 'type': 'DRUG', 'description': '48 hours IV infusion of nesiritide on insulin sensitivity (IS) measured by two-step hyperinsulinemic euglycemic clamp in obese nondiabetic insulin resistant subjects.', 'armGroupLabels': ['Obese nondiabetic insulin resistant subjects- Panel A', 'Obese nondiabetic insulin resistant subjects- Panel B']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '48 hours of placebo.', 'armGroupLabels': ['Obese nondiabetic insulin resistant subjects- Panel A', 'Obese nondiabetic insulin resistant subjects- Panel B']}]}, 'contactsLocationsModule': {'locations': [{'zip': '32804', 'city': 'Orlando', 'state': 'Florida', 'country': 'United States', 'facility': 'Translational Research Institute for Metabolism and Diabetes', 'geoPoint': {'lat': 28.53834, 'lon': -81.37924}}], 'overallOfficials': [{'name': 'Richard Pratley, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Translational Reseach institute for Metabolism and Diabetes'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'AdventHealth Translational Research Institute', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}