Effect of Recombinant Human Growth Hormone (rhGH) on Abdominal Fat and Cardiovascular Risk in Obese Girls

Study Overview
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Brief Summary
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Teenagers and adults who are overweight or obese have an increase in fat in the abdomen, which increases their risk for diabetes and heart disease. Reducing abdominal fat is important to reduce risk for diabetes and for heart disease. Overweight teenagers also have low levels of growth hormone compared to normal weight teenagers, and teenagers with the lowest growth hormone levels also have the greatest abdominal fat. In children who are unable to make growth hormone for other reasons, giving back growth hormone leads to a decrease in abdominal fat. We are studying whether giving growth hormone in small doses to overweight teenagers can change body composition. We hypothesize that growth hormone will cause abdominal fat to decrease and reduce the risk markers for diabetes and heart disease.

Official Title
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Effect of rhGH Administration on Visceral Adiposity and Markers of Cardiovascular Risk in Obese Adolescent Girls: Phase 2

Conditions
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Obesity

Intervention / Treatment
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* Drug: recombinant human growth hormone (rhGH)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescent girls 13-21 years old with bone age ≥ 14 years Overweight girls: Body Mass Index (BMI) greater than the 95th percentile for age Waist/Hip ratio ≥ 0.85 Insulin Like Growth Factor -1 (IGF-1) below -0.5 standard deviations (SD) for pubertal stage or age Exclusion Criteria: Pregnancy (positive pregnancy test) prior to enrollment in the study Significant weight gain or loss within 3 months of study (more than 5 kg) Use of medications that affect GH or cortisol levels (such as estrogen including oral contraceptive pills, oral glucocorticoids) Use of medications such as Meridian and Orlistat Presence of diabetes mellitus Uncontrolled Thyroid disorders Chronic renal insufficiency Participation in another simultaneous medical investigation or trial Active neoplasm or history of cancer Prader-Willi syndrome History of scoliosis if bone age is <15 years Hypersensitivity to rhGH or constituents of the injections

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: recombinant human growth hormone<br>Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. | Drug: recombinant human growth hormone (rhGH)<br>* Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.<br>|
| Placebo Comparator: Placebo<br>Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. | Drug: Placebo<br>* Placebo will be administered by daily subcutaneous injections. Sham increases will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visceral and Subcutaneous Abdominal Adipose Tissue Over 6 Months | Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) were assessed using single slice MR imaging (MRI) | Baseline and 6 months | 
| Changes in Lipid Panel | Lipid profile will be obtained using established methods. Total Cholesterol, Triglycerides, LDL and HDL measurements will be obtained at baseline, and then at the six-month visits to determine the rate at which lipid measures change with rhGH therapy | Baseline and 6 months | 
| Change in High-sensitivity C-reactive Protein (Hs-CRP) Over 6 Months | As a marker of cardiovascular risk, hs-CRP will be assessed at baseline and 6 months to assess the rate at which hs-CRP levels change with rhGH therapy. | Baseline and 6 months | 
| Change in Soluble Intercellular Adhesion Molecule-1 (sICAM) Over 6 Months | Soluble intercellular adhesion molecule-1 (sICAM) was used as a surrogate marker of cardiovascular risk | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score | Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. A 2-hour Oral Glucose Tolerance Test (OGTT) using 1.75 gram/kilogram of oral glucose (maximum 75 gram) will be performed at baseline and six months after administration of rhGH/placebo/ no therapy. Fasting insulin and glucose will be used to determine HOMA-IR: [fasting glucose (mmol/l) x fasting insulin (µU/ml)]/22.5] | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Adolescent, Insulin resistance, Growth hormone, Visceral fat, Adolescent obesity