Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Study Overview
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Brief Summary
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Fatty liver disease is an increasing problem in overweight and obese young adults. The purpose of this study is to test the effect of growth hormone on liver fat in obese young adults ages 18-29y with increased liver fat.

Detailed Description
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Non-alcoholic fatty liver disease (NAFLD) is a significant health problem in obese adolescents. Obese children and adolescents have significant reductions in growth hormone secretion, and we hypothesize that augmenting growth hormone in this population will decrease liver fat. Growth hormone inhibits hepatic de novo lipogenesis, which is an important source of hepatic lipid. Patients with pituitary GH deficiency have a higher prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) than the general population, and replacement of GH in these individuals reduces signs of liver damage. The purpose of this study is to test the hypothesis that growth hormone treatment will decrease liver fat quantity in young adults who begin the trial with more than 5% liver fat measured by magnetic resonance spectroscopy.

Official Title
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Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Conditions
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NAFLD

Intervention / Treatment
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* Drug: somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males and Females ages 18-29yo BMI ≥95th percentile and/or ≥30kg/m^2 Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS) IGF-1 standard deviation score (SDS) < 0 Exclusion criteria: Alcohol consumption of >14 drinks per week (Females) or >21 drinks per week (Males) Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) >7% or fasting glucose ≥126mg/dL Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline visit Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis hemoglobin < 11.0 g/dL or weight < 50kg aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x upper limit of normal (ULN), total bilirubin > ULN, positive hepatitis B surface antigen (sAg), or positive hepatitis C antibody Routine magnetic resonance imaging (MRI) exclusion criteria (including weight >450 pounds) Use of weight-loss medications or previous weight loss surgery Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an appropriate form of contraception during the study Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or exam Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year Change in lipid lowering or anti-hypertensive medications within 3 months of screening Change in vitamin E or ursodiol <6 months before screen; subjects on stable doses of Vitamin E and/or Ursodiol for ≥6 months will be eligible. History of malignancy or active malignancy History of hypopituitarism, head irradiation or any other condition or chronic illness known to affect the GH axis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 29 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth hormone<br>Somatropin given by daily subcutaneous injection. Dose will begin at 1mg and be titrated based on insulin-like growth factor 1 (IGF-1) levels. | Drug: somatropin<br>* Norditropin (growth hormone) given by injection using a pen-device<br>|
| No Intervention: No treatment<br>(no study treatment - observation only) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hepatic Fat Fraction | change in hepatic fat fraction between baseline and 24 weeks as measured by hydrogen magnetic resonance spectroscopy | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aspartate Aminotransferase (AST) | change in AST between baseline and 24 weeks | 24 weeks | 
| Change in Alanine Aminotransferase (ALT) | change in ALT between baseline and 24 weeks | 24 weeks | 
| Change in Gamma Glutamyl Transferase (GGT) | change in GGT between baseline and 24 weeks | 24 weeks | 
| Change in Visceral Adipose Tissue | Change in visceral adipose tissue cross-sectional area at the 4th lumbar vertebra as measured by magnetic resonance imaging between baseline and 24 weeks | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, adolescence, fatty liver, growth hormone