Metabolism of Fibrinogen and Apolipoprotein B-100 in Childhood Obesity and Cardiovascular Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 主要终点
- Fibrinogen
研究概览
简要总结
Since obesity and plasma fibrinogen levels are important CVD risk factors in the adults, and since childhood obesity is a major risk factor for adult obesity and also because it is not established whether or not this is due to an increase in the FSR of fibrinogen, the investigators set up the studies with the following specific aims:
- To investigate the metabolism of fibrinogen and VLDL apoB-100, CVD risk factors, in childhood obesity by measuring their fractional synthetic rate (FSR) compared to lean age and sex matched controls
- To determine the outcome of a three month non-pharmacological intervention (physical exercise combined with controlled diet) to reduce weight on the FSR of fibrinogen and apoB-100
- To determine the relationship between FSR of fibrinogen and IL-6 in obese children and its potential implications on CVD before and after the non-pharmacological intervention
- To determine other CVD risk factors, PAI-1 levels, D-Dimer concentration, homocysteine, insulin, free fatty acid, HDL & LDL cholesterol and blood pressure in response to weight reduction (as consequence of a combined program of diet and exercise).
详细描述
A. SPECIFIC AIMS:
Evidence from the literature suggests that:
- childhood onset of obesity increases the risk of obesity and cardiovascular disease (CVD) in adulthood;
- plasma fibrinogen and apolipoprotein B-100 (apoB-100) levels are elevated in obesity;
- elevated levels of plasma fibrinogen and apolipoprotein B-100 (apoB-100) are major independent risk factors for CVD in adults;
- raised plasma fibrinogen levels in obese children and/adolescents could be a major factor responsible for CVD morbidity and mortality in adulthood;
- a low level of physical activity is associated with a high level of plasma fibrinogen in adults;
- physical training and controlled diet have been proved to be non-pharmacological ways to improve hemostatic function in adults, thereby reducing heart disease risk. Despite these evidences the mechanism of these changes remain unclear. A better understanding of the mechanism of these changes will lead to more directed therapies to reduce these risk factors early in life.
The increased plasma concentrations of fibrinogen (and/or other proteins) is decided by the equilibrium between two dynamic processes in the body, namely, synthesis and degradation rates of these proteins. Therefore, elevated levels of fibrinogen must be a consequence of:
- increased fibrinogen synthesis;
- decreased fibrinogen degradation or
- a contribution of both.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Obese: BMI ≥30 kg/m2
- •Lean (controls): BMI ≤ 25 kg/m2) age 14 to 18 years and Tanner stage matched
- •Ability to understand and cooperate with the procedures
- •Signed informed consent from subjects and parents
排除标准
- •Medications such as Beta-adrenergic blockers, steroids and other drugs known to affect protein metabolism
- •Heart disease
- •Chronic liver disease
- •Chronic renal disease
- •Active malignancy
- •Alcoholism or drug abuse
- •Inter-current illness over the 7 days before the study
- •Surgery in the past 3 months
结局指标
主要结局
Fibrinogen
时间窗: 12 weeks
Plasma concentration measured by nephelometry
Fractional synthesis rate of fibrinogen
时间窗: 12 weeks
Stable isotope mass spectrometry
Protein turnover
时间窗: 12 weeks
Stable isotope mass spectrometry
次要结局
- Fat mass(12 weeks)
- Fat free mass(12 weeks)
研究者
Babu Balagopal
Director, Biomedical Analysis Laboratory
Nemours Children's Clinic