Study of Serum Markers for Cardiovascular Risk in Obese Youth and Impact of Lifestyle and Medication Intervention

Not Applicable

Completed

Conditions: Obesity

Interventions: Drug: Metformin
Behavioral: Dietary modification with caloric restriction
Behavioral: Establishment of exercise protocol

Registration Number: NCT00139477

Lead Sponsor: Nemours Children's Clinic

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

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 #1.
Must have higher values than normal for certain blood tests related to heart disease that were measured in Protocol #1.

Exclusion Criteria

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Diet/Exercise only, then Diet/Exercise plus Metformin	Metformin	Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
Diet/Exercise only, then Diet/Exercise plus Metformin	Dietary modification with caloric restriction	Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
Diet/Exercise only, then Diet/Exercise plus Metformin	Establishment of exercise protocol	Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).
Diet/Exercise plus Metformin, then Diet/Exercise only	Dietary modification with caloric restriction	Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
Diet/Exercise plus Metformin, then Diet/Exercise only	Establishment of exercise protocol	Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
Diet/Exercise plus Metformin, then Diet/Exercise only	Metformin	Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months	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	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	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	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).