Clinical trial

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.

Name

04-032

Description

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.

Trial arms

Trial start

2003-11-01

Estimated PCD

2009-05-01

Trial end

2011-09-01

Status

Completed

Treatment

Metformin

Metformin, 250mg by mouth twice a day with meals will be started and if tolerated increased to 500mg twice a day in 3 days in those less than 12 years old and titrated further to 1000mg twice a day if tolerated.

Arms:

Diet/Exercise only, then Diet/Exercise plus Metformin, Diet/Exercise plus Metformin, then Diet/Exercise only

Dietary modification with caloric restriction

The life style intervention changes will include a hypocaloric diet representing at least a 500 kcal/day reduction based on their dietary histories and Resting Energy Expenditure (REE) determined by the initial calorimetry.

Arms:

Diet/Exercise only, then Diet/Exercise plus Metformin, Diet/Exercise plus Metformin, then Diet/Exercise only

Establishment of exercise protocol

Participants will attend the Fitness Center 3 times per week and supervised by an exercise technician or exercise specialist. Exercise will be individually prescribed for each participant based on their functional abilities. Exercise will consist of 5-10 minutes for warm up and stretching, followed by 15-30 minutes of cardiovascular exercise (i.e. treadmill, bicycle ergometer, rower, nustep, etc), 10-20 minutes of strength training (supervised using weight stack equipment), and 5-10 minutes of cool down and stretching. As children typically do not need an exercise prescription based on heart rate, we will familiarize them with perceived exertion scales and monitor that they are exercising in the moderate to hard range of perception of effort. Participants will be started at 15 minutes of cardiovascular exercise and 10 minutes of strength training exercise, progressing by 2-3 minutes every week until 30 and 20 minutes is achieved for each respectively.

Arms:

Diet/Exercise only, then Diet/Exercise plus Metformin, Diet/Exercise plus Metformin, then Diet/Exercise only

Size

Primary endpoint

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

Baseline and 6 months

Change From Baseline in Fibrinogen at 6 Months

Baseline and 6 months

Change From Baseline in Interleukin 6 (IL-6) at 6 Months

Baseline and 6 months

Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at 6 Months

Baseline and 6 months

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 66, 'type': 'ACTUAL'}}

Updated at

2023-04-18

1 organization

1 drug

1 indication

Organization

Nemours Children's Clinic

Drug

Metformin

Indication

Obesity