Understanding the Effects of Therapeutic Intervention on Cardiovascular Risk Markers, Insulin Resistance, and Intra-Hepatic Fat Contents in Obese Children at High Risk for the Metabolic Syndrome.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months
研究概览
简要总结
In Protocol #2, we will select 30 obese pubertal and 30 obese prepubertal subjects with an abnormal cytokine profile (i.e. fibrinogen and/or hsCRP concentration greater than or equal to 2 Standard Deviations (SD) above the mean established in our lab for lean controls in Protocol #1). They will be randomly assigned to either lifestyle intervention (diet/exercise) or diet/exercise plus metformin for 6 months. After the 6 month evaluation the subjects will cross over the treatment arms, i.e., those that were doing diet/exercise intervention only will add metformin, those that were doing the diet/exercise plus metformin will discontinue the metformin and continue with diet/exercise changes only. Intrahepatic fat contents will be measured as well.
The investigators hypothesize that obese children in these age groups will have increased cardiovascular risk related to their obese state before reaching the currently defined criteria of metabolic syndrome.
The investigators hypothesize that these cardiovascular risks can be reduced with lifestyle and drug interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ages 7-18 years.
- •Greater than the 95th percentile body mass index for their age and gender.
- •Children are in Tanner Stage I or IV or V.
- •Normal Blood Pressure.
- •Normal fasting glucose.
- •Normal lipids.
- •Menstruating girls must have completed their most recent period at least 2 weeks prior to blood draw.
- •No recent illness, no chronic illnesses, no routine medications, no smoking or alcohol intake.
- •Must pass the screening test done in Protocol #
- •Must have higher values than normal for certain blood tests related to heart disease that were measured in Protocol #1.
排除标准
- •Chronic active illnesses.
- •Recent illnesses.
- •Use of routine medications, vitamins, herbal remedies, oral contraceptive pills, or other over the counter medications within 4 weeks of blood draw.
- •History of recent or chronic smoking.
- •Currently pregnant.
- •Impaired fasting glucose.
- •Dyslipidemia.
- •Actively in puberty.
- •Weight greater than 300 pounds.
- •Metal in the abdomen.
- •History of being overweight greater than 5 years.
研究组 & 干预措施
Diet/Exercise only, then Diet/Exercise plus Metformin
Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
干预措施: Metformin (Drug)
Diet/Exercise only, then Diet/Exercise plus Metformin
Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
干预措施: Dietary modification with caloric restriction (Behavioral)
Diet/Exercise only, then Diet/Exercise plus Metformin
Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
干预措施: Establishment of exercise protocol (Behavioral)
Diet/Exercise plus Metformin, then Diet/Exercise only
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
干预措施: Metformin (Drug)
Diet/Exercise plus Metformin, then Diet/Exercise only
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
干预措施: Dietary modification with caloric restriction (Behavioral)
Diet/Exercise plus Metformin, then Diet/Exercise only
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
干预措施: Establishment of exercise protocol (Behavioral)
结局指标
主要结局
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months
时间窗: Baseline and 6 months
Value at 6 months minus value at baseline. HsCRP is an acute phase protein which is a sensitive marker for systemic inflammation. HsCRP concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA), with an hsCRP lower sensitivity of 0.156 mg/L.
Change From Baseline in Fibrinogen at 6 Months
时间窗: Baseline and 6 months
Value at 6 months minus value at baseline. Fibrinogen is a hepatic-derived factor directly involved in clotting and in the viscosity characteristics of blood flow. It binds to platelets and contributes to their aggregation, promotes fibrin formation and is also an acute phase reactant that is increased in inflammatory states. Fibrinogen concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA).
Change From Baseline in Interleukin 6 (IL-6) at 6 Months
时间窗: Baseline and 6 months
Value at 6 months minus value at baseline. IL-6 is a pro-inflammatory cytokine thought to produce a state of low-grade inflammation in obese individuals. IL-6 stimulates hepatic production of C-reactive protein (CRP), an acute phase protein which is a sensitive marker for systemic inflammation. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA; R\&D Systems, Minneapolis, MN, USA).
Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at 6 Months
时间窗: Baseline and 6 months
Value at 6 months minus value at baseline. PAI-1 is the primary physiological inhibitor of fibrinolysis and proteolysis. High PAI-1 levels have been linked to thrombosis and fibrosis, insulin resistance and obesity. PAI-1 was measured by ELISA (American Diagnostica, Stamford, CT, USA).
次要结局
未报告次要终点
研究者
Nelly Mauras
Principal investigator
Nemours Children's Clinic