BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Difference in level of B-type Natriuretic Peptide (BNP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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;
- •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.
研究组 & 干预措施
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).
干预措施: Nesiritide (Drug)
Saline
Saline infusion
干预措施: Saline (Drug)
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).
干预措施: Nesiritide (Drug)
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).
干预措施: Nesiritide (Drug)
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).
干预措施: Nesiritide (Drug)
结局指标
主要结局
Difference in level of B-type Natriuretic Peptide (BNP)
时间窗: 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).
次要结局
- Differences in the expression of NPRC(Day 7)
- 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)
- Difference in responses of lean and obese subjects(Days -2, 7, 14)
- Determine whether short term infusion of rhBNP increases metabolic rate and/or fat oxidation(Day 7)