DiabetesPhase 1BNP3NCT03234751
Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects
A Phase 1 study testing Continous IV infusion of Nesiritide and Hyperinsulinemic euglycemic clamp in people with Diabetes, run by AdventHealth Translational Research Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- Continous IV infusion of Nesiritide and Hyperinsulinemic euglycemic clamp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2017to 19 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 40-65 years inclusive
- Men and women
- Able to provide written, informed consent
- Weight stable (± 3 kg) during the 3 months prior to enrollment
- BMI ≥ 30 kg/m2; body weight ≤ 106 kg
- Resting blood pressure ≥ 110/60 mmHg and ≤ 150/100 mmHg
Who cannot join
- Known coronary artery disease, angina or heart failure
- Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose >125mg/dL)
- Bleeding disorders
- Hemoglobin level < 12.5 g/dL for women; < 13.0 g/dL for men
- Acute or chronic infections
- Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal)
Show all 20Show fewer
- Severe asthma or chronic obstructive pulmonary disease
- Renal insufficiency (creatinine > 1.6 mg/dL)
- Prior bariatric surgery
- Inflammatory bowel disease or malabsorption
- Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
- Psychiatric or eating disorders
- Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders
- Active rheumatoid arthritis or other inflammatory rheumatic disorder
- Pregnant or nursing women
- Presence of clinically significant abnormalities on electrocardiogram
- Smoking (within the last 3 months)
- Known hypersensitivity to nesiritide or any of its excipients
- Poor intravenous access
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Translational Research Institute for Metabolism and Diabetes
Orlando, Florida, 32804
About this study
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.
- Conditions
- Diabetes
- Being tested
- Continous IV infusion of Nesiritide, Hyperinsulinemic euglycemic clamp, Placebo
- Keywords
- human B-type natriuretic peptide
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continous IV infusion of NesiritideDrug
Nesiritide (fhBNP) administered by continuous IV infusion during 48 hours.
Hyperinsulinemic euglycemic clampDrug
48 hours IV infusion of nesiritide on insulin sensitivity (IS) measured by two-step hyperinsulinemic euglycemic clamp in obese nondiabetic insulin resistant subjects.
PlaceboDrug
48 hours of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Obese nondiabetic insulin resistant subjects- Panel A | Active comparator | IV nesiritide 3 pmol/kg/min or placebo for nesiritide Receives: Drug: Continous IV infusion of Nesiritide; Drug: Hyperinsulinemic euglycemic clamp; Drug: Placebo |
| Obese nondiabetic insulin resistant subjects- Panel B | Active comparator | IV nesiritide 2 pmol/kg/min or placebo for nesiritide Receives: Drug: Continous IV infusion of Nesiritide; Drug: Hyperinsulinemic euglycemic clamp; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
IV infusion of nesiritide at a 3pmol/kg rate
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.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start13 Jul 2017
- Primary completion24 Sep 2018
- Study completion19 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- AdventHealth Translational Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Pratley, MD, Principal investigator, Translational Reseach institute for Metabolism and Diabetes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234751
- Sponsor's protocol ID
- TRIMDFH 1081082
- Acronym
- BNP3
- Status last verified
- Mar 2020
- First submitted
- 18 Jul 2017
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 18636063Poirier 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.
PubMed 16380542Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.
PubMed 15181019Aneja 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.
PubMed 14749502Mancia 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.
PubMed 17414649Goodfriend 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.
PubMed 10440591Sarzani 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.
PubMed 8957740Wang 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.
PubMed 14769680Potter 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.
PubMed 16291870Khan 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.
PubMed 21849523Chen-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.
PubMed 21059435Bertoni 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.
PubMed 21959345Tsukamoto 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.
PubMed 19477358Pivovarova 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.
PubMed 22419733Miyashita 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.
PubMed 19690065
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects
- ClinicalTrials.gov ID
- NCT03234751
- Acronym / sponsor ID
- BNP3 / TRIMDFH 1081082
- Conditions
- Diabetes
- Keywords
- human B-type natriuretic peptide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- AdventHealth Translational Research InstituteUniversity, hospital or other
- Study start
- 13 Jul 2017 (actual)
- Primary completion
- 24 Sep 2018 (actual)
- Study completion
- 19 Feb 2020 (actual)
- First posted
- 31 Jul 2017 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Obese nondiabetic insulin resistant subjects- Panel A | Active comparator | Drug: Continous IV infusion of Nesiritide, Drug: Hyperinsulinemic euglycemic clamp, Drug: PlaceboIV nesiritide 3 pmol/kg/min or placebo for nesiritide |
| Obese nondiabetic insulin resistant subjects- Panel B | Active comparator | Drug: Continous IV infusion of Nesiritide, Drug: Hyperinsulinemic euglycemic clamp, Drug: PlaceboIV nesiritide 2 pmol/kg/min or placebo for nesiritide |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 40-65 years inclusive
- Men and women
- Able to provide written, informed consent
- Weight stable (± 3 kg) during the 3 months prior to enrollment
- BMI ≥ 30 kg/m2; body weight ≤ 106 kg
Key exclusion criteria (20 listed)
- Known coronary artery disease, angina or heart failure
- Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose >125mg/dL)
- Bleeding disorders
- Hemoglobin level < 12.5 g/dL for women; < 13.0 g/dL for men
- Acute or chronic infections
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 |
|---|---|---|
| Continous IV infusion of NesiritideNesiritide (fhBNP) administered by continuous IV infusion during 48 hours. | Drug | Obese nondiabetic insulin resistant subjects- Panel A, Obese nondiabetic insulin resistant subjects- Panel B |
| Hyperinsulinemic euglycemic clamp48 hours IV infusion of nesiritide on insulin sensitivity (IS) measured by two-step hyperinsulinemic euglycemic clamp in obese nondiabetic insulin resistant subjects. | Drug | Obese nondiabetic insulin resistant subjects- Panel A, Obese nondiabetic insulin resistant subjects- Panel B |
| Placebo48 hours of placebo. | Drug | Obese nondiabetic insulin resistant subjects- Panel A, Obese nondiabetic insulin resistant subjects- Panel B |
Primary outcome
IV infusion of nesiritide at a 3pmol/kg rate
Time frame: 48 hours
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Background: PubMed 18636063Centers 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.
- Background: PubMed 16380542Poirier 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.
- Background: PubMed 15181019Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.
- Background: PubMed 14749502Aneja 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.
- Background: PubMed 17414649Mancia 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.
- Background: PubMed 10440591Goodfriend 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.
- Background: PubMed 8957740Sarzani 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.
- Background: PubMed 14769680Wang 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.
- Background: PubMed 16291870Potter 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.
- Background: PubMed 21849523Khan 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.
- Background: PubMed 21059435Chen-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.
- Background: PubMed 21959345Bertoni 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.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Richard Pratley, MD principal investigator
Translational Reseach institute for Metabolism and Diabetes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Continous IV infusion of Nesiritide and Hyperinsulinemic euglycemic clamp in people with Diabetes, run by AdventHealth Translational Research Institute 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 6 inclusion and 20 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: finished, as of the sponsor's last update on 10 Mar 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IV infusion of nesiritide at a 3pmol/kg rate (time frame: 48 hours). 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 NCT03234751, which also lists 23 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 10 Mar 2020.