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BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects

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ClinicalTrials.gov Identifier: NCT01977859
Recruitment Status : Completed
First Posted : November 7, 2013
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Sanford-Burnham Medical Research Institute
Information provided by (Responsible Party):
Translational Research Institute for Metabolism and Diabetes, Florida

Tracking Information
First Submitted Date  ICMJE October 31, 2013
First Posted Date  ICMJE November 7, 2013
Last Update Posted Date February 14, 2018
Study Start Date  ICMJE November 2013
Actual Primary Completion Date February 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2013)
Difference in level of B-type Natriuretic Peptide (BNP) [ Time Frame: Days -2, 7, 14 ]
Blood samples will be obtained at baseline, during the infusion and after the termination of the infusion for measurement of levels of recombinant human BNP (rhBNP) and N-terminal pro-brain natriuretic peptide (NTpro-BNP).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2013)
  • Differences in the expression of NPRC [ Time Frame: Day 7 ]
    Natriuretic peptides Type-A and Type-C (NPRA,NPRC) expression will be measured by RT-PCR in subcutaneous abdominal adipose tissue samples obtained by percutaneous biopsy prior to infusion of rhBNP and related to the Metabolic Clearance Rate (MCR) for BNP
  • Determine whether short term infusion of rhBNP increases metabolic rate and/or fat oxidation [ Time Frame: Day 7 ]
    Energy expenditure and substrate oxidation rates will be measured for 30 min at baseline, prior to the infusion of BNP, then continuously during the rhBNP infusion in a 3200 Liters Flex Room Calorimeter respiratory chambers.
  • determine whether short term infusion of rhBNP alters gene expression in subcutaneous adipose tissue and skeletal muscle in a pattern consistent with activation of thermogenic pathways [ Time Frame: Day 7 ]
    Adipose tissue will be obtained from subcutaneous abdominal sites and skeletal muscle from the vastus lateralis by percutaneous biopsy prior to and after the infusion of rhBNP. The expression of Uncoupling Protein 1 (UCP1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), cytochrome c and PR domain containing 16 (PRDM16) (a significant factor in brown adipogenesis) will be measured by Reverse transcription polymerase chain reaction (RT-PCR).
  • Difference in responses of lean and obese subjects [ Time Frame: Days -2, 7, 14 ]
    Blood pressure and heart rate will be monitored at 10 minute intervals with an automated blood pressure cuff to measure physiological response and to monitor hemodynamic status and safety. Fractional sodium excretion, cGMP and creatinine, and total urine output in response to the rhBNP infusion will be compared in lean and obese subjects. Blood samples will be obtained at baseline, during the infusion and after termination of the infusion for measurement of cyclic Guanosine 3´,5´-Cyclic Monophosphate (cGMP), Plasma Renin Activity (PRA), Aldosterone (ALD), Renin (REN), NE, glucose, insulin, Non-essential fatty acid (NEFA), glycerol, adiponectin, C-Reactive Protein (CRP), Tumor Necrosis Factor- α (TNF-α) and other cytokines/chemokines.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects
Official Title  ICMJE BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects
Brief Summary The purpose of this study is to collect data to help researchers better understand the various causes of obesity, which may lead to the development of new obesity treatment options.
Detailed Description Obesity is major metabolic health concern and the potential beneficial effects of natriuretic peptides, specifically B-type natriuretic peptide (BNP) on adipocyte biology, energy expenditure and body weight could be of great significance. This study will provide insight into the mechanisms of dysregulation of the natriuretic peptides system in obesity and will contribute to delineate the roles and the clinical importance of BNP in the treatment of obesity.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Obesity
  • Cardiovascular Disease
  • Hypertension
  • Diabetes
Intervention  ICMJE
  • Drug: Nesiritide
  • Drug: Saline
Study Arms  ICMJE
  • Placebo Comparator: Saline
    Saline infusion
    Intervention: Drug: Saline
  • Active Comparator: Nesiritide 1.0
    Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 1.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).
    Intervention: Drug: Nesiritide
  • Active Comparator: Nesiritide 2.0
    Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 2.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).
    Intervention: Drug: Nesiritide
  • Active Comparator: Nesiritide 4.0
    Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 4.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).
    Intervention: Drug: Nesiritide
  • Active Comparator: Nesiritide 8.0
    Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 8.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).
    Intervention: Drug: Nesiritide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2017)
4
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2013)
48
Actual Study Completion Date  ICMJE February 28, 2017
Actual Primary Completion Date February 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18-65 years, inclusive
  • Men and women
  • Able to provide written, informed consent
  • Weight stable (± 3 kg) during the 3 months prior to enrollment
  • BMI ≤ 25 kg/m2 for lean subjects or ≥ 30 kg/m2 for obese subjects

Exclusion Criteria:

  • 1) Diagnosed with any of the following co-morbidities: a) coronary artery disease, angina or heart failure, b) diabetes, c) bleeding disorders, d) infections, e) hepatitis and/or cirrhosis, f) severe asthma or Chronic obstructive pulmonary disease (COPD), g) renal insufficiency, h) bariatric surgery, i) inflammatory bowel disease or malabsorption, j) cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ), k) psychiatric or eating disorders, l) untreated or inadequately controlled thyroid or other endocrine disorders, m) active rheumatoid arthritis or other inflammatory rheumatic disorder
  • Pregnant or nursing women
  • Presence of clinically significant abnormalities on electrocardiogram;
  • Smoking
  • 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 COX-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phentermine or other weight loss or anorectic agents.
  • Your blood pressure at your screening visit is less than or equal to 100/60 or greater than or equal to 160/100.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01977859
Other Study ID Numbers  ICMJE TRIMDFH 472930
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Translational Research Institute for Metabolism and Diabetes, Florida
Study Sponsor  ICMJE Translational Research Institute for Metabolism and Diabetes, Florida
Collaborators  ICMJE Sanford-Burnham Medical Research Institute
Investigators  ICMJE
Principal Investigator: Richard E. Pratley, MD AdventHealth
PRS Account Translational Research Institute for Metabolism and Diabetes, Florida
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP