NAFLD
Conditions
Keywords
obesity, adolescence, fatty liver, growth hormone
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.
Interventions
DRUGsomatropin
Norditropin (growth hormone) given by injection using a pen-device
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 29 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hepatic Fat Fraction | 24 weeks | change in hepatic fat fraction between baseline and 24 weeks as measured by hydrogen magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aspartate Aminotransferase (AST) | 24 weeks | change in AST between baseline and 24 weeks |
| Change in Alanine Aminotransferase (ALT) | 24 weeks | change in ALT between baseline and 24 weeks |
| Change in Gamma Glutamyl Transferase (GGT) | 24 weeks | change in GGT between baseline and 24 weeks |
| Change in Visceral Adipose Tissue | 24 weeks | Change in visceral adipose tissue cross-sectional area at the 4th lumbar vertebra as measured by magnetic resonance imaging between baseline and 24 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
somatropin: Norditropin (growth hormone) given by injection using a pen-device | 13 |
| No Treatment (no study treatment - observation only) | 11 |
| Total | 24 |
Baseline characteristics
| Characteristic | Growth Hormone | No Treatment | Total |
|---|---|---|---|
| Age, Continuous | 25 years STANDARD_DEVIATION 3 | 23 years STANDARD_DEVIATION 4 | 24 years STANDARD_DEVIATION 4 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic (independent of race) | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Other or more than 1 race | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 6 Participants | 15 Participants |
| Region of Enrollment United States | 13 participants | 11 participants | 24 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 11 |
| other Total, other adverse events | 9 / 13 | 1 / 11 |
| serious Total, serious adverse events | 1 / 13 | 0 / 11 |
Outcome results
Primary
Change in Hepatic Fat Fraction
change in hepatic fat fraction between baseline and 24 weeks as measured by hydrogen magnetic resonance spectroscopy
Time frame: 24 weeks
Population: all available data used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Hepatic Fat Fraction | -3.0 Percent (Hepatic fat fraction, percent) | Standard Deviation 5.2 |
| No Treatment | Change in Hepatic Fat Fraction | 0.3 Percent (Hepatic fat fraction, percent) | Standard Deviation 3.5 |
Secondary
Change in Alanine Aminotransferase (ALT)
change in ALT between baseline and 24 weeks
Time frame: 24 weeks
Population: all available data used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Alanine Aminotransferase (ALT) | -2 units per liter | Standard Deviation 9 |
| No Treatment | Change in Alanine Aminotransferase (ALT) | 1 units per liter | Standard Deviation 8 |
Secondary
Change in Aspartate Aminotransferase (AST)
change in AST between baseline and 24 weeks
Time frame: 24 weeks
Population: all available data used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Aspartate Aminotransferase (AST) | -3 units per liter | Standard Deviation 9 |
| No Treatment | Change in Aspartate Aminotransferase (AST) | -1 units per liter | Standard Deviation 4 |
Secondary
Change in Gamma Glutamyl Transferase (GGT)
change in GGT between baseline and 24 weeks
Time frame: 24 weeks
Population: all available data used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Gamma Glutamyl Transferase (GGT) | -9 units per liter | Standard Deviation 30 |
| No Treatment | Change in Gamma Glutamyl Transferase (GGT) | 5 units per liter | Standard Deviation 9 |
Secondary
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
Time frame: 24 weeks
Population: all available data used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Visceral Adipose Tissue | -6 square centimeters | Standard Deviation 50 |
| No Treatment | Change in Visceral Adipose Tissue | 6 square centimeters | Standard Deviation 24 |