Clinical trial NCT02726542: Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents
Official title: Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: NAFLD
Keywords: obesity
adolescence
fatty liver
growth hormone
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-04-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion criteria:

1. Males and Females ages 18-29yo
2. BMI ≥95th percentile and/or ≥30kg/m\^2
3. Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS)
4. IGF-1 standard deviation score (SDS) \< 0

Exclusion criteria:

1. Alcohol consumption of \>14 drinks per week (Females) or \>21 drinks per week (Males)
2. Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) \>7% or fasting glucose ≥126mg/dL
3. Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline visit
4. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis
5. hemoglobin \< 11.0 g/dL or weight \< 50kg
6. 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
7. Routine magnetic resonance imaging (MRI) exclusion criteria (including weight \>450 pounds)
8. Use of weight-loss medications or previous weight loss surgery
9. Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an appropriate form of contraception during the study
10. Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or exam
11. Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year
12. Change in lipid lowering or anti-hypertensive medications within 3 months of screening
13. 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.
14. History of malignancy or active malignancy
15. History of hypopituitarism, head irradiation or any other condition or chronic illness known to affect the GH axis

Primary outcomes:
measure: Change in Hepatic Fat Fraction
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: 24 weeks
measure: Change in Alanine Aminotransferase (ALT)
timeFrame: 24 weeks
measure: Change in Gamma Glutamyl Transferase (GGT)
timeFrame: 24 weeks
measure: Change in Visceral Adipose Tissue
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Takara Stanley, MD
role: PRINCIPAL_INVESTIGATOR
References: