Cardiovascular Disease, Diabetes, Hypertension, Obesity
Conditions
Keywords
B-type Natriuretic Peptide, Metabolism, Insulin infusion
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.
Interventions
DRUGNesiritide
DRUGSaline
Sponsors
Sanford-Burnham Medical Research Institute
AdventHealth Translational Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in level of B-type Natriuretic Peptide (BNP) | 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
| Measure | Time frame | Description |
|---|---|---|
| Differences in the expression of NPRC | 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 | 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 | 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 | 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. |
Countries
United States
Outcome results
None listed