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Trial · Interventional

CompletedNot applicableResults postedRegistry data

Tesamorelin Effects on Liver Fat and Histology in HIV

NCTNCT02196831 (opens ClinicalTrials.gov in a new tab)Other id1U01AI115711Other idU01AI115711

Overview

Status
Completed
Phase
Not applicable
Enrollment
61 participants (actual)
Sponsor
Massachusetts General Hospital · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
1 Jul 2015
Primary completion
16 Jan 2019
Completion
24 Jul 2019
First posted
22 Jul 2014 (estimated)
Last update posted
27 Jan 2020
Conditions
Human Immunodeficiency Virus (HIV) · Nonalcoholic Fatty Liver Disease (NAFLD) · Nonalcoholic Steatohepatitis (NASH)

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201520162017201820192020
  1. N/A

    Tesamorelin Effects on Liver Fat and Histology in HIV

    NCT02196831

    1 Jul 2015 to 24 Jul 2019

Registry summary

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.

Interventions

  • tesamorelinDrug
  • PlaceboDrug

Arms2

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy

    Time frame · change between baseline and 12 months

    Registry description

    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 outcomes(3)
  1. Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score

    Time frame · change between baseline and 12 months

    Registry description

    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.

  2. Change in Alanine Aminotransferase (ALT)

    Time frame · change from baseline to 12 months

    Registry description

    change (value at 12 months minus value at baseline)

  3. Change in Aspartate Aminotransferase (AST)

    Time frame · change from baseline to 12 months

    Registry description

    change (value at 12 months minus value at baseline)

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· change between baseline and 12 months

Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy

GroupValue (percent (hepatic fat fraction))Spread
Tesamorelin-4.76.6
Placebo0.04.1
Secondary and other outcome results(3)
Secondary outcomeMean· change between baseline and 12 months

Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score

GroupValue (score on a scale, NAFLD activity score)Spread
Tesamorelin-0.161.34
Placebo0.131.03
Secondary outcomeMean· change from baseline to 12 months

Change in Alanine Aminotransferase (ALT)

GroupValue (units/liter (U/L))Spread
Tesamorelin-211
Placebo515
Secondary outcomeMean· change from baseline to 12 months

Change in Aspartate Aminotransferase (AST)

GroupValue (units/liter (U/L))Spread
Tesamorelin-211
Placebo-24

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther 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. tesamorelin0 / 314 / 3129 / 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 tesamorelin0 / 302 / 3029 / 30
Open Label Tesamorelin Armfollowing the 12 month double-blind period, all subjects received open-label tesamorelin 2mg daily subcutaneously for 6 months.1 / 433 / 4335 / 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

Studies3

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2021

17 results

Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.

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

Rights unknown17 results

PubMed tag: none · 2021

7 results

Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach.

Fourman et al. 2021Scientific reportscited by 8

PMID 34006921PMC8131688DOI 10.1038/s41598-021-89966-yPUB-34006921

CC BY7 results

Indexing hint: Randomized controlled trial · 2019

6 results

Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial.

Stanley et al. 2019The lancet. HIVcited by 66

PMID 31611038PMC6981288DOI 10.1016/s2352-3018(19)30338-8PUB-31611038

Rights unknown6 results

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedStanley TL, Fourman LT, Zheng I, McClure CM, Feldpausch MN, Torriani M, Corey KE, Chung RT, Lee H, Kleiner DE, Hadigan CM, Grinspoon SK. Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e520-e533. doi: 10.1210/clinem/dgaa792. PMID 33125080

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 70 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria: * Men and women 18-70yo * HIV-infection and treatment with a stable antiretroviral regimen for ≥ 6 months * Hepatic steatosis as demonstrated by liver fat fraction ≥5% on 1H-MRS * Hepatitis C antibody negative, or, if Hepatitis C antibody positive, either: a) known clinical disease, successful therapy ≥1 year prior to baseline and undetectable HCV RNA, or b) HCV resolved spontaneously and undetectable HCV RNA. Hepatitis B surface antigen negative at screen visit * For females ≥50yo, negative mammogram within 1 year of baseline visit * If use of Vitamin E ≥400 IU daily (in any formulation), stable dose for ≥6 months prior to study. Exclusion criteria: * Heavy alcohol use defined as consumption of more than 20g daily for women or more than 30g daily for men for at least 3 consecutive months over the past 5 years * Use of insulin or thiazoledinediones (TZDs), or HbA1c ≥7%. Individuals with mild diabetes that is well-controlled with diet and/or oral anti-diabetic agents besides TZDs will be included. Use of oral anti-diabetics must have been stable for ≥6 months prior to study entry. * Known diabetic retinopathy. * Known cirrhosis, or Child-Pugh score ≥7, stage 4 fibrosis on biopsy, or clinical evidence of cirrhosis or portal hypertension on imaging or exam. * Chronic corticosteroid use except intermittent use of topical steroid creams and/or prior short-term physiologic corticosteroid use in the ≤ 6 months prior to baseline visit * Chronic use of methotrexate, amiodarone, or tamoxifen * Known diagnosis of Alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis * Use of GH or GHRH within the past 1 year * Change in lipid lowering or anti-hypertensive regimen within 3 months of screening * HgB \< 11.0 g/dL, CD4 \< 100 th/mm3, or HIV viral load \> 400 copies/mL * Active malignancy * For men, history of prostate cancer or evidence of prostate malignancy by PSA \> 5 ng/mL * Severe chronic illness judged by the investigator to present a contraindication to participation * History of hypopituitarism, head irradiation or any other condition known to affect the GH axis * Use of physiologic testosterone (men) or estrogen or progesterone (women) unless stable use for a year or more prior to study entry * Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip * Previous weight loss surgery * For women, positive pregnancy test performed in a CLIA certified laboratory using a test with a sensitivity of at least 25mIU/mL, or breastfeeding. * Known hypersensitivity to tesamorelin or mannitol * Unwillingness to abstain from the conception process during the study (i.e., must agree not to participate in an active attempt to become pregnant or impregnate, donate sperm, or participate in in vitro fertilization) * Unwillingness to use one (for males) or two (for females) reliable methods of contraception while engaging in heterosexual intercourse during the study. Acceptable methods for women include hormonal contraception (estrogen/progesterone or progesterone-only formulations) if stable for a year or more prior to study entry, intrauterine device, or barrier methods (condom, or diaphragm with spermicide). Acceptable methods for males include condom use. This requirement does not apply to women who have been post-menopausal for at least 24 consecutive months or have undergone surgical sterilization, or to men who have undergone surgical sterilization or have documented azoospermia. * Not willing or able to adhere to dose schedules and required procedures per protocol

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