Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 131
Healthy volunteers: no

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).

Detailed description:

Arms:
arm 1: Growth hormone (somatropin) administered by daily injection at starting dose of 0.3 mg daily for women and 0.2 mg daily for men, with dose titration for goal IGF-1 in the upper quartile of normal for age. arm 2: Placebo will be administered by daily injection in this double blind study design. Sham dosing will be performed to maintain blinding.

Interventions: intervention 1: Growth hormone intervention 2: Placebo
Intervention descriptions: intervention 1: growth hormone, Genotropin (Pfizer) intervention 2: placebo with identical drug pen delivery device and packaging as Genotropin (Pfizer)

Protocol document:
Prot_000.pdf: 































SAP_001.pdf: 
Growth Hormone and Intrahepatic Lipid Content in Patients with 
Nonalcoholic Fatty Liver Disease 
 
NCT# 02217345 
 
Version Date: 2/17/2022 
 
Statistical Analysis Plan 
 
 


 
A. Study endpoints  
 
 
Primary Endpoint: Change in intrahepatic lipid accumulation over 6 months in the GH vs placebo group.  
 
Secondary Endpoints: Change in the following endpoints over 6 months in the GH vs placebo group. 
1. Liver function tests 
2. Adipokines:  leptin and adiponectin 
3. Inflammatory markers: hsCRP, IL-6 and TNF alpha receptors 
4. Measures of insulin resistance 
5. Abdominal fat compartments 
6. NAFLD Fibrosis Score 
7. ELF Score 
8. Liver stiffness by Fibroscan 
9. Liver inflammation and fibrosis by Liver MultiScan 
 
B. Experimental approach:  
A total of approximately 65 otherwise healthy subjects with NAFLD and relatively low IGF-1 levels will be 
enrolled after a screening visit at which study eligibility will be determined with a history, physical exam, 
blood work, IGF-1 level and hemoglobin A1C. Eligible subjects will be randomized to receive GH or placebo. 
GH reserve will be characterized at baseline. Subjects will be studied for 6 months. We plan to enroll up to 
65 individuals and will attempt to replace subjects who have dropped out of the study to ensure 50 
completers at 6 months. 
 
C. Statistical power and Analysis 
Power Calculation:  A total of approximately 65 patients will enter this two-treatment parallel-design study 
with enrollment of up to 50 completers. With 40 completers, the probability is increased to 90 percent that 
the study will detect a treatment difference in percent intrahepatic lipid content at a two-sided 0.05 
significance level, if the true difference between treatment with GH and placebo is 6.5%. With 50 
completers, the probability is 90 percent that the study will detect a treatment difference in percent 
intrahepatic lipid content at a two-sided 0.05 significance level, if the true difference between treatment with 
GH and placebo is 5.7%. This is based on the assumption that the standard deviation of the response 
variable is 6.1% as observed in Wong et. al.1 Studies available for power calculations include all comers with 
NAFLD, and our study population is restricted to those without diabetes who are more likely to have a lower 
severity of disease.  Additionally, there is recognized variability in the natural history of NAFLD, particularly 
in early stage disease. For these reasons, we will attempt to replace subjects who have dropped out of the 
study to ensure 50 completers at 6 months.  
 
Data Analysis Plan: We will pool data from men and women using a random slopes model; we will consider 
a model where each study subject has a random slope and intercept. The primary analysis is a pooled 
analysis of treatment effect across gender with weights equaling the frequency of men and women in the 
sample. A secondary analysis will test for the significance of the treatment-gender interaction on the rate of 
change of intrahepatic liver fat and all other endpoints. For all analyses, an intent-to-treat analysis will be 
performed.  
 
 
 
(1) Wong VW, Chan RS, Wong GL, Cheung BH, Chu WC, Yeung DK, Chim AM, Lai JW, Li LS, Sea MM, Chan FK, Sung 
JJ, Woo J, Chan HL. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a 
randomized controlled trial. Journal of hepatology. 2013;59(3):536-542.