Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

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.

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Drug: somatropin

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 29 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Growth hormone; 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; Norditropin (growth hormone) given by injection using a pen-device
No Intervention: No treatment; (no study treatment - observation only)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Takara Stanley, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2017
• Primary Completion (Actual): April 2, 2020
• Study Completion (Actual): April 2, 2020

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: obesity; fatty liver; growth hormone; adolescence
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2016p-000657

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No