Abdominal Obesity, Cardiovascular Inflammation, and Effects of a Growth Hormone Releasing Hormone Analogue to Reduce Inflammation
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- aortic "target to background ratio" (Aortic TBR)
研究概览
简要总结
Obesity is strongly associated with risk of cardiovascular disease (CVD). Data increasingly suggest that visceral adipose tissue (VAT) accumulation -- or increased abdominal fat -- is particularly deleterious to cardiovascular health, but further study is needed to test this idea. Increased abdominal fat may also be associated with lower secretion of a hormone called growth hormone (GH), which helps the body burn fat. The current study aims to carefully characterize relationships between abdominal fat and CVD. In addition, by using a medication called growth hormone releasing hormone, which is a strategy to reduce abdominal fat, the investigators will test the hypothesis that abdominal fat contributes uniquely to increased arterial inflammation.
In the first part of this study, the investigators will investigate both lean (healthy weight) individuals and individuals with increased abdominal fat. The investigators will study their body composition, cardiovascular risk measures, insulin sensitivity, and growth hormone dynamics, with the hypothesis that abdominal fat, independent of general obesity, will be strongly associated with arterial wall thickening and atherosclerotic inflammation. The investigators will assess arterial wall thickness, plaque morphology, and atherosclerotic inflammation, and the investigators will determine associations between these variables and regional fat accumulation, with particular attention to abdominal fat.
The second, treatment part of the study will be only for individuals with increased abdominal fat who are found to have low growth hormone secretion. In that part of the study, the investigators will test the effects of a growth hormone releasing hormone (GHRH) analogue to reduce abdominal fat and, consequently, reduce arterial inflammation. The investigators hypothesize that abdominal fat reduction, independent of changes in growth hormone, will reduce arterial inflammation and arterial wall thickness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Inclusion Criteria for Lean Controls:
- •Men and women age 18-55y
- •BMI > 18.5 and < 25 kg/m2
- •Waist circumference < 102 cm in men and <88cm in women
- •Inclusion criteria for Abdominal Obesity:
- •Men and women age 18-55y
- •BMI ≥ 30kg/m2
- •Abdominal obesity as defined by waist circumference ≥ 102 cm in men and ≥ 88 cm in women
- •Relative GH deficiency as demonstrated by peak GH to arginine/GHRH stimulation test of < 9mcg/L (for treatment portion only)
- •Negative age-appropriate screening for cancer performed by primary care physician (e.g., negative mammogram if F > 50yo) (For treatment portion only)
- •Exclusion criteria for all subjects:
- •Obesity due to known secondary causes
- •Use of weight-lowering drugs or previous weight loss surgery
- •Use of gonadal steroids, GH, GHRH, glucocorticoids, megesterol acetate, antidiabetic agents, or any other hormonal medication judged by the investigator to be inappropriate within the past 6 months. Use of physiologic testosterone replacement will be allowed.
- •Known coronary artery disease or peripheral vascular disease, or any history of stroke or significant chest pain
- •Known auto-immune or inflammatory disease
- •Any surgery or significant injury (including fracture or other trauma) within the past 6 months
- •Hemoglobin < 11g/dL, fasting glucose > 126mg/dL, creatinine <1.5mg/dL, or AST > 2.5x upper limit of normal
- •FSH > 20 IU/L (women only)
- •Positive urine pregnancy test, actively seeking pregnancy, or breastfeeding
- •Prior history of pituitary disease, pituitary surgery, or head irradiation, or any other condition known to affect pituitary function
- •Infectious illness in the past 3 months, or chronic infectious illness
- •Allergy to iodine containing contrast media
- •Active illicit drug use
- •For women of childbearing potential, failure to use an acceptable form of non-hormonal birth control
- •Active malignancy: For the treatment part of the study, all active malignancy will be excluded. For the observational part of the study (which involves no intervention) basal cell carcinoma and low grade cervical or anal intraepithelial neoplasms will be allowed.
- •History of colon cancer (treatment part only)
研究组 & 干预措施
Growth Hormone Releasing Hormone
Growth Hormone Releasing Hormone analogue, 2mg subcutaneously every day for 12 months.
干预措施: Tesamorelin (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
aortic "target to background ratio" (Aortic TBR)
时间窗: 12 months
aortic target-to-background ratio is a measure of the inflammation in the wall of the aorta that is made by positron emission tomography (PET) scanning in conjunction with computed tomography (CT) scanning.
次要结局
未报告次要终点
研究者
Steven K. Grinspoon, MD
Professor of Medicine, Harvard Medical School
Massachusetts General Hospital