Growth Hormone Treatment on Phosphocreatine Recovery in Obesity

Not Applicable

Completed

Brief Summary: Obesity is associated with reduced growth hormone (GH) secretion. Reduced GH secretion in obesity is associated with increased cardiovascular disease risk. However, it is not yet known how reduced GH increases cardiovascular disease risk in obesity. The investigators hypothesize that reduced GH contributes to dysfunction of the mitochondria. Therefore, the investigators hypothesize that treatment of obese subjects with reduced GH secretion with GH will improve mitochondrial function and that this improvement in mitochondrial function will contribute, in part, to the effects of GH to improve metabolic parameters in obesity. The investigators propose to study skeletal muscle mitochondria in obese subjects with reduced GH secretion using magnetic resonance spectroscopy and muscle biopsies before and after treatment with GH.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Obesity due to a known secondary cause (Cushing's syndrome, hypothyroidism, etc) or a history of gastric bypass procedure.
Subjects who have a known history of diabetes, fasting blood sugar >125 mg/dl or using any anti-diabetic drugs.
Use of Aspirin, Clopidogrel (Plavix), Warfarin (Coumadin) or other anti-coagulants
Subjects on testosterone, glucocorticoids, anabolic steroids, GHRH, GH or IGF-1 within 3 months of enrollment.
Changes in lipid lowering or anti-hypertensive regimen within 3 months of screening
History of pituitary tumor, hypopituitarism, pituitary surgery, pituitary/brain radiation or traumatic brain injury or any other condition known to affect the GH axis.
Severe chronic illness including HIV, active malignancy or history of colon cancer.
Hemoglobin < 9.0 g/dL, SGOT > 2.5 x upper limit normal, Creatinine >1.5 mg/dL, or PSA >5 ng/ml.
Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.
Contraindications to MRI scanning.

Arm && Interventions

Group	Intervention	Description
Growth Hormone	Growth hormone treatment	-

Primary Outcome Measures

Name	Time	Method
Phosphocreatine Recovery	12-weeks	The primary objective of this study is to determine the effects of growth hormone on mitochondrial function as assessed by 31P-MRS in obese subjects with reduced GH secretion. Mitochondrial function was represented by ViPCr, a measure of phosphocreatine recovery after sub-maximal exercise. Univariate regression analyses was performed to assess the relationship between the change in skeletal muscle IGF-1 mRNA after 12 weeks treatment with rhGH to change in ViPCr.

Secondary Outcome Measures

Name	Time	Method
Change in Circulating IGF-1 Concentration	Baseline and 12-weeks	Change in circulating IGF-1 from Baseline to 12-weeks is reported.
Change in Skeletal Muscle IGF-1 Gene Expression	Baseline and 12-weeks	Change in skeletal muscle IGF-1 gene mRNA expression from Baseline to 12-weeks is reported.
Change in Body Composition	Baseline and 12-weeks	Change in waist circumference from Baseline to 12-weeks is reported.
Change in Inflammatory Marker	Baseline and 12-weeks	Change in high sensitivity C-reactive protein (hsCRP) from Baseline to 12-weeks is reported.
Change in Insulin Sensitivity	Baseline and 12-weeks	Change in fasting glucose from Baseline to 12-weeks is reported.
Change in Phosphocreatine Recovery	Baseline and 12-weeks	Change in phosphocreatine recovery, represented by ViPCr, from Baseline to 12-weeks is reported.