Nonalcoholic Fatty Liver Disease (NAFLD)
Conditions
Brief summary
Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is an increasingly recognized complication of obesity, with prevalence estimates of about 30% of individuals in the United States. A subset of these will develop progressive disease in the form of nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver failure. NAFLD is expected to be the most common indication for liver transplantation by the year 2020. We hypothesize that growth hormone (GH) replacement will decrease intrahepatic lipid accumulation as quantified by 1H magnetic resonance spectroscopy (1H-MRS).
Interventions
DRUGGrowth hormone
growth hormone, Genotropin (Pfizer)
DRUGPlacebo
placebo with identical drug pen delivery device and packaging as Genotropin (Pfizer)
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18 - 65 yr 2. NAFLD defined as demonstration of hepatic steatosis by imaging or biopsy in absence of significant alcohol consumption and other causes of hepatic steatosis. If liver imaging or biopsy has not been performed clinically, liver ultrasound will be performed as part of the screening visit.
Exclusion criteria
1. Serum creatinine \> 2 times the upper limit of normal 2. History of cancer, except for non-melanoma skin cancers 3. Active carpel tunnel syndrome 4. Diabetes mellitus, defined as a hemoglobin A1C \>6.5 or use of any medications prescribed to treat hyperglycemia. The exception is that the use of metformin is acceptable in patients whose HbA1c has been =\<6.0 on two visits and whose weight has remained stable for six months. 5. Contraindications to magnetic resonance imaging (MRI). 6. Pregnancy or desire to become pregnant. Participants of reproductive age must agree to use contraception. 7. Breastfeeding 8. Aspartate and aminotransferase levels \>10x upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months. | 6 months | Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months. | 6 months | Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through hospital-wide and community advertisements between 2017-2021. Recruitment techniques included posting advertisements on the internet (i.e. Craigslist and Facebook) and on the Massachusetts General Hospital's clinical trial recruitment website.
Pre-assignment details
Of the 131 people who signed a consent form, 78 were unable to participate due to various reasons including meeting ineligibility criteria. The 53 subjects who remained were randomized to one of two arms. One subject discontinued after randomization but before any baseline procedures were completed, leaving 52 subjects with available baseline data.
Participants by arm
| Arm | Count |
|---|---|
| Growth Hormone Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range. | 26 |
| Placebo Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Growth Hormone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 26 Participants | 51 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 12 | 46 years STANDARD_DEVIATION 12 | 46 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 24 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 20 Participants | 39 Participants |
| Region of Enrollment United States | 26 participants | 26 participants | 52 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 15 / 24 | 11 / 25 |
| serious Total, serious adverse events | 1 / 24 | 0 / 25 |
Outcome results
Primary
Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.
Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months. | -5.2 percent liver fat | Standard Deviation 10.5 |
| Placebo | Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months. | 3.8 percent liver fat | Standard Deviation 6.9 |
Secondary
Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.
Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months. | -0.8 mg/L | Standard Deviation 0.9 |
| Placebo | Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months. | 0.3 mg/L | Standard Deviation 1.7 |