Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Mass General Brigham

Status and phase: Completed; Early Phase 1

Conditions: NAFLD

Treatments: Drug: somatropin

Study type: Interventional

Funder types: Other

Identifiers

NCT02726542

2016p-000657

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 29 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Growth hormone

Experimental group

Description:

Somatropin given by daily subcutaneous injection. Dose will begin at 1mg and be titrated based on insulin-like growth factor 1 (IGF-1) levels.

Treatment:

Drug: somatropin

No treatment

No Intervention group

Description:

(no study treatment - observation only)