BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects

AdventHealth Translational Research Institute

Status and phase: Completed; Phase 1

Conditions: Hypertension; Diabetes; Obesity; Cardiovascular Disease

Treatments: Drug: Nesiritide; Drug: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT01977859

TRIMDFH 472930

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

4 participants in 5 patient groups, including a placebo group

Saline

Placebo Comparator group

Description:

Saline infusion

Treatment:

Drug: Saline

Nesiritide 1.0

Active Comparator group

Description:

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).

Treatment:

Drug: Nesiritide

Nesiritide 2.0

Active Comparator group

Description:

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).

Treatment:

Drug: Nesiritide

Nesiritide 4.0

Active Comparator group

Description:

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).

Treatment:

Drug: Nesiritide

Nesiritide 8.0

Active Comparator group

Description:

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).

Treatment:

Drug: Nesiritide