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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo.
recombinant human growth hormone	recombinant human growth hormone (rhGH)	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo.

Primary Outcome Measures

Name	Time	Method
Change in High-sensitivity C-reactive Protein (Hs-CRP) Over 6 Months	Baseline and 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.
Change in Visceral and Subcutaneous Abdominal Adipose Tissue Over 6 Months	Baseline and 6 months	Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) were assessed using single slice MR imaging (MRI)
Changes in Lipid Panel	Baseline and 6 months	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
Change in Soluble Intercellular Adhesion Molecule-1 (sICAM) Over 6 Months	Baseline and 6 months	Soluble intercellular adhesion molecule-1 (sICAM) was used as a surrogate marker of cardiovascular risk

Secondary Outcome Measures

Name	Time	Method
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score	Baseline and 6 months	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\]