Human Immunodeficiency Virus (HIV)NCT02196831
Tesamorelin Effects on Liver Fat and Histology in HIV
A study testing tesamorelin in people with Human Immunodeficiency Virus (HIV) and Nonalcoholic Fatty Liver Disease (NAFLD), run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Human Immunodeficiency Virus (HIV), Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- What is being tested?
- tesamorelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2015to 24 Jul 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health
Bethesda, Maryland, 20892
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant
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.
- Conditions
- Human Immunodeficiency Virus (HIV), Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- Being tested
- tesamorelin, Placebo
- Keywords
- Human immunodeficiency virus (HIV), Nonalcoholic fatty liver disease (NAFLD), Nonalcoholic steatohepatitis (NASH), Growth hormone releasing hormone, tesamorelin
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tesamorelinDrug
Also called Egrifta
PlaceboDrug
inactive substance that looks like tesamorelin
| Study group | Role | What they receive |
|---|---|---|
| Tesamorelin | Experimental | 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. Receives: Drug: tesamorelin |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy
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.
Measured: change between baseline and 12 months
Secondary outcomes (3)
Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score
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.
Measured: change between baseline and 12 months
Change in Alanine Aminotransferase (ALT)
change (value at 12 months minus value at baseline)
Measured: change from baseline to 12 months
Change in Aspartate Aminotransferase (AST)
change (value at 12 months minus value at baseline)
Measured: change from baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2014 (estimated)
- Study start1 Jul 2015
- Primary completion16 Jan 2019
- Study completion24 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven K. Grinspoon, MD, Massachusetts General Hospital
- Investigators
- Steven K Grinspoon, MD, Principal investigator, MGH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02196831
- Sponsor's protocol ID
- 1U01AI115711
- Other IDs
- U01AI115711
- Status last verified
- Jan 2020
- First submitted
- 18 Jul 2014
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec;6(12):e821-e830. doi: 10.1016/S2352-3018(19)30338-8. Epub 2019 Oct 11.
PubMed 31611038Fourman LT, Stanley TL, Billingsley JM, Sui SJH, Feldpausch MN, Boutin A, Zheng I, McClure CM, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Chung RT, Grinspoon SK. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach. Sci Rep. 2021 May 18;11(1):10485. doi: 10.1038/s41598-021-89966-y.
PubMed 34006921Stanley TL, Fourman LT, Wong LP, Sadreyev R, Billingsley JM, Feldpausch MN, Zheng I, Pan CS, Boutin A, Lee H, Corey KE, Torriani M, Kleiner DE, Chung RT, Hadigan CM, Grinspoon SK. 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. Clin Infect Dis. 2021 Aug 16;73(4):621-630. doi: 10.1093/cid/ciab019.
PubMed 33852720Stanley 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.
PubMed 33125080
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant
- ClinicalTrials.gov ID
- NCT02196831
- Acronym / sponsor ID
- 1U01AI115711
- Conditions
- Human Immunodeficiency Virus (HIV), Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- Keywords
- Human immunodeficiency virus (HIV), Nonalcoholic fatty liver disease (NAFLD), Nonalcoholic steatohepatitis (NASH), Growth hormone releasing hormone, tesamorelin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 16 Jan 2019 (actual)
- Study completion
- 24 Jul 2019 (actual)
- First posted
- 22 Jul 2014 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tesamorelin | Experimental | Drug: tesamorelintesamorelin 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 | Placebo comparator | Drug: Placeboplacebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tesamorelinAlso: Egrifta | Drug | Tesamorelin |
| Placeboinactive substance that looks like tesamorelin | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score
Time frame: change between baseline and 12 months
Change in Alanine Aminotransferase (ALT)
Time frame: change from baseline to 12 months
Change in Aspartate Aminotransferase (AST)
Time frame: change from baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31611038Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec;6(12):e821-e830. doi: 10.1016/S2352-3018(19)30338-8. Epub 2019 Oct 11.
- Derived from this study: PubMed 34006921Fourman LT, Stanley TL, Billingsley JM, Sui SJH, Feldpausch MN, Boutin A, Zheng I, McClure CM, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Chung RT, Grinspoon SK. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach. Sci Rep. 2021 May 18;11(1):10485. doi: 10.1038/s41598-021-89966-y.
- Derived from this study: PubMed 33852720Stanley TL, Fourman LT, Wong LP, Sadreyev R, Billingsley JM, Feldpausch MN, Zheng I, Pan CS, Boutin A, Lee H, Corey KE, Torriani M, Kleiner DE, Chung RT, Hadigan CM, Grinspoon SK. 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. Clin Infect Dis. 2021 Aug 16;73(4):621-630. doi: 10.1093/cid/ciab019.
- Derived from this study: PubMed 33125080Stanley 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven K Grinspoon, MD principal investigator
MGH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tesamorelin in people with Human Immunodeficiency Virus (HIV) and Nonalcoholic Fatty Liver Disease (NAFLD), run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy (time frame: change between baseline and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02196831, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.