Tesamorelin Effects on Liver Fat and Histology in HIV
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02196831|
Recruitment Status : Completed
First Posted : July 22, 2014
Results First Posted : January 13, 2020
Last Update Posted : January 27, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus (HIV) Nonalcoholic Fatty Liver Disease (NAFLD) Nonalcoholic Steatohepatitis (NASH)||Drug: tesamorelin Drug: Placebo||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant|
|Actual Study Start Date :||July 1, 2015|
|Actual Primary Completion Date :||January 16, 2019|
|Actual Study Completion Date :||July 24, 2019|
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.
Other Name: Egrifta
Placebo Comparator: 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.
inactive substance that looks like tesamorelin
- Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy [ Time Frame: 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.
- Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score [ Time Frame: 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:
- steatosis, graded from 0 [<5% liver fat] to grade 3 [>66% liver fat]
- lobular inflammation, graded from 0 [no foci of inflammation] to 3 [>4 foci per 200x field]
- 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 Alanine Aminotransferase (ALT) [ Time Frame: change from baseline to 12 months ]change (value at 12 months minus value at baseline)
- Change in Aspartate Aminotransferase (AST) [ Time Frame: change from baseline to 12 months ]change (value at 12 months minus value at baseline)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02196831
|United States, Maryland|
|National Institutes of Health|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Steven K Grinspoon, MD||MGH|