Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy
| Group | Value (percent (hepatic fat fraction)) | Spread |
|---|---|---|
| Tesamorelin | -4.7 | 6.6 |
| Placebo | 0.0 | 4.1 |
Trial · Interventional
CompletedNot applicableResults postedRegistry dataUnited States
1 trial · 1 completed · 1 with posted results
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Experimental
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.
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.
Outcomes the sponsor listed as primary.
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: 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 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)
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (percent (hepatic fat fraction)) | Spread |
|---|---|---|
| Tesamorelin | -4.7 | 6.6 |
| Placebo | 0.0 | 4.1 |
| Group | Value (score on a scale, NAFLD activity score) | Spread |
|---|---|---|
| Tesamorelin | -0.16 | 1.34 |
| Placebo | 0.13 | 1.03 |
| Group | Value (units/liter (U/L)) | Spread |
|---|---|---|
| Tesamorelin | -2 | 11 |
| Placebo | 5 | 15 |
| Group | Value (units/liter (U/L)) | Spread |
|---|---|---|
| Tesamorelin | -2 | 11 |
| Placebo | -2 | 4 |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Tesamorelin (Double-blind Phase)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. tesamorelin | 0 / 31 | 4 / 31 | 29 / 31 |
| Placebo (Double-blind Phase)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. Placebo: inactive substance that looks like tesamorelin | 0 / 30 | 2 / 30 | 29 / 30 |
| Open Label Tesamorelin Armfollowing the 12 month double-blind period, all subjects received open-label tesamorelin 2mg daily subcutaneously for 6 months. | 1 / 43 | 3 / 43 | 35 / 43 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies that cite this trial.
3 studies on this page
Indexing hint: Randomized controlled trial · 2021
Stanley et al. 2021Clinical infectious diseases : an official publication of the Infectious Diseases Society of Americacited by 11
PMID 33852720PMC8366828DOI 10.1093/cid/ciab019PUB-33852720
PubMed tag: none · 2021
Fourman et al. 2021Scientific reportscited by 8
PMID 34006921PMC8131688DOI 10.1038/s41598-021-89966-yPUB-34006921
Indexing hint: Randomized controlled trial · 2019
Stanley et al. 2019The lancet. HIVcited by 66
PMID 31611038PMC6981288DOI 10.1016/s2352-3018(19)30338-8PUB-31611038
References listed at the registry that are not in PepBank. They link to PubMed.
Who could join, as posted.
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