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Completed

NCT Number: NCT01977859

BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Nesiritide

Drug

Saline

Drug

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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

  2. 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.

  3. 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).

  4. 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.

Sponsors and collaborators

Lead sponsor

AdventHealth Translational Research Institute

Other

Collaborators

  • Sanford-Burnham Medical Research Institute

Registry information

Important dates

Study start
2013
Primary completion
2016
Study completion
2017
First posted
Nov 7, 2013
Registry last updated
Feb 14, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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