Tesamorelin Effects on Liver Fat and Histology in HIV

Not Applicable

Completed

Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
Human Immunodeficiency Virus (HIV)
Nonalcoholic Steatohepatitis (NASH)

Brief Summary: Liver disease is one of the leading co-morbidities of human immunodeficiency virus (HIV) infection, and nonalcoholic fatty liver disease (NAFLD) is present in approximately 30-40% of patients with HIV infection. Nonalcoholic steatohepatitis (NASH) is a more severe form of NAFLD in which increased liver fat is also accompanied by inflammation, cellular damage, and fibrosis.

NAFLD is most prevalent in patients who also have increased visceral adiposity, and our group has previously shown that HIV-infected individuals with increased visceral adiposity generally have decreased growth hormone secretion. Tesamorelin is a growth hormone releasing hormone (GHRH) analogue that increases endogenous growth hormone secretion. Tesamorelin is FDA-approved for the reduction of visceral fat in HIV-infected individuals. In a previous study, treatment with tesamorelin in HIV-infected individuals selected for abdominal adiposity reduced liver fat. The current study is designed to test the effect of tesamorelin on liver fat and steatohepatitis in HIV-infected individuals who have NAFLD. The investigators hypothesize that tesamorelin will reduce liver fat and will also ameliorate the inflammation, fibrosis, and hepatocellular damage seen in conjunction with NASH.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.
Tesamorelin	tesamorelin	tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.

Primary Outcome Measures

Name	Time	Method
Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy	change between baseline and 12 months	change (value at 12 months minus value at baseline). Hepatic fat fraction is a standardized measure used to describe the percent fat in the liver. As it is determined by spectroscopy, it is quantified by the area under the lipid peak, standardized to the total area under the (lipid peak + water peak). Using 1-H Magnetic resonance spectroscopy to quantify liver fat in this manner was first described by Longo R et al., Invest Radiol, 1993, 28(4):297-302.

Secondary Outcome Measures

Name	Time	Method
Change in Alanine Aminotransferase (ALT)	change from baseline to 12 months	change (value at 12 months minus value at baseline)
Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score	change between baseline and 12 months	change (value at 12 months minus value at baseline). The nonalcoholic fatty liver disease (NAFLD) activity score is a standardized histological quantification of NAFLD severity designed and validated by the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner DE et al., Hepatology, 2005, 41(6):1313-1321). The score is the sum of three semi-quantitative histological grades: 1. steatosis, graded from 0 \[\<5% liver fat\] to grade 3 \[\>66% liver fat\] 2. lobular inflammation, graded from 0 \[no foci of inflammation\] to 3 \[\>4 foci per 200x field\] 3. hepatocellular ballooning, graded from 0 \[no ballooning\] to 2 \[many cells/prominent ballooning\] The "total" NAFLD activity score, a sum of the three components below, ranges from 0 to 8, with a higher score generally representing greater severity of NAFLD/nonalcoholic steatohepatitis.
Change in Aspartate Aminotransferase (AST)	change from baseline to 12 months	change (value at 12 months minus value at baseline)

Locations (2): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
National Institutes of Health
🇺🇸
Bethesda, Maryland, United States