Growth Hormone Treatment on Phosphocreatine Recovery in Obesity

Study Overview
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Brief Summary
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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.

Official Title
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The Effects of Short Term Growth Hormone Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity

Conditions
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Obese, Growth Hormone Secretion Abnormality

Intervention / Treatment
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* Drug: Growth hormone treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men age 18-60 years old BMI ≥ 30 kg/m2 Waist circumference ≥ 102 cm Peak GH value of ≤ 4.2 μg/l on standard GHRH-arginine stimulation test 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth Hormone<br> | Drug: Growth hormone treatment<br>* Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phosphocreatine Recovery | 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. | 12-weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth hormone, GH, Obesity, Mitochondrial function, reduced growth hormone secretion