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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Growth Hormone Releasing Hormone Analog to Improve Nonalcoholic Fatty Liver Disease and Associated Cardiovascular Risk

Overview

Status
Completed
Phase
Phase 2
Enrollment
51 participants (actual)
Sponsor
Massachusetts General Hospital · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
17 Jan 2019
Primary completion
10 Jul 2024
Completion
10 Jan 2025
First posted
18 Dec 2017
Last update posted
20 Nov 2025
Conditions
Non-Alcoholic Fatty Liver Disease · Obesity · Obesity, Abdominal · Liver Fat · Fatty Liver

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202220242026
  1. Ph 2

    Growth Hormone Releasing Hormone Analog to Improve Nonalcoholic Fatty Liver Disease and Associated Cardiovascular Risk

    NCT03375788

    17 Jan 2019 to 10 Jan 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Nonalcoholic fatty liver disease (NAFLD) is common in individuals with obesity and is a significant threat to public health, because it can lead to impaired liver function and liver failure. Growth hormone is a hormone produced in the pituitary gland that helps regulate metabolism and growth. Individuals with obesity, on average, secrete less growth hormone than individuals without obesity. There are data to suggest that growth hormone may help to reduce the amount of fat in the liver, and may also reduce inflammation in the liver, both of which would be helpful to individuals with NAFLD. The purpose of this study is to investigate whether treatment with a drug called tesamorelin, which is a growth hormone releasing hormone analogue, will decrease liver fat and improve liver inflammation and scarring in obese individuals with NAFLD.

Interventions

  • TesamorelinDrug
  • Identical PlaceboDrug

Arms2

  • Experimental

    Tesamorelin

    tesamorelin (brand name Egrifta) 2mg daily given subcutaneously

  • Placebo comparator

    Placebo

    identical placebo given subcutaneously daily

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Liver Fat Content

    Time frame · change from baseline to 12 months

    Registry description

    Liver Fat Content as measured by hydrogen-magnetic resonance spectroscopy. All available data used; data not available for 1 participant in tesamorelin group and 3 participants in placebo group.

Secondary outcomes(4)
  1. NAFLD Activity Score

    Time frame · change from baseline to 12 months

    Registry description

    Nonalcoholic Fatty Liver Disease Activity Score (NAS, scored between 0-8, with higher indicating more severe disease) from liver biopsy. All available data used; data not available for 3 participants in placebo group and 1 participant in tesamorelin group.

  2. Low Density Lipoprotein (LDL) Cholesterol

    Time frame · change from baseline to 12 months

    Registry description

    All available data utilized. Data not available for 2 participants in tesamorelin group and 3 participants in placebo group.

  3. C-reactive Protein

    Time frame · change from baseline to 12 months

    Registry description

    All available data utilized. Data not available for 2 participants in placebo group.

  4. Fibrosis Score

    Time frame · change from baseline to 12 months

    Registry description

    fibrosis score from liver biopsy; all available data used - data not available for 1 participant in tesamorelin group and 3 participants in placebo group. Fibrosis stage scored from 0-4, where 0 indicates no fibrosis and 4 indicates most severe fibrosis, which is cirrhosis.

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 outcomeMedian· change from baseline to 12 months

Liver Fat Content

GroupValue (percent change in hepatic fat fraction)
Tesamorelin-5.3
Placebo3.6
Secondary and other outcome results(4)
Secondary outcomeMedian· change from baseline to 12 months

NAFLD Activity Score

GroupValue (units on a scale)
Tesamorelin0
Placebo0
Secondary outcomeMean· change from baseline to 12 months

Low Density Lipoprotein (LDL) Cholesterol

GroupValue (milligrams per deciliter)Spread
Tesamorelin-5.727
Placebo-0.716
Secondary outcomeMean· change from baseline to 12 months

C-reactive Protein

GroupValue (milligrams per liter (mg/L))Spread
Tesamorelin-0.94.2
Placebo0.04.1
Secondary outcomeMedian· change from baseline to 12 months

Fibrosis Score

GroupValue (units on a scale)
Tesamorelin0
Placebo0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Double-blind Phase: Tesamorelintesamorelin (brand name Egrifta) 2mg daily given subcutaneously for first 12 months Tesamorelin: Tesamorelin F4 formulation 1.4mg daily0 / 262 / 2622 / 26
Double-blind Phase: Placeboidentical placebo given subcutaneously daily for first 12 months Identical Placebo: Placebo injection daily0 / 253 / 2515 / 25
Open Label Phaseall patients receiving open-label tesamorelin from months 12-180 / 300 / 3016 / 30

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

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Men and women 18-65yo 2. Body mass index (BMI) ≥ 30kg/m2, or, for participants with known steatohepatitis, BMI ≥ 25kg/m2 3. Hepatic steatosis as demonstrated by either a) Grade 1+ steatosis on a liver biopsy performed within 12 months of the baseline visit, without \>10% reduction in body weight or addition of medications to treat fatty liver, or b) liver fat fraction ≥5% on hydrogen-magnetic resonance spectroscopy (1H-MRS) 4. Hepatitis C antibody and Hepatitis B surface antigen negative. Subjects without known history of Hepatitis C or Hepatitis C treatment who have a positive Hepatitis C antibody but a negative hepatitis C viral load will also be eligible. 5. For females ≥50yo, negative mammogram within 1 year of baseline 6. If use of vitamin E ≥400 international units daily, stable dose for ≥6 mos 7. Up to date with colon cancer screening recommended by the participant's primary care physician, using whatever methodology the primary physician recommends. This will be ascertained by self-report. (If a participant does not have a primary care physician, we will discuss that colon cancer screening is recommended, typically starting at age 50y, and refer the participant to primary care through Partners if s/he desires.) Exclusion Criteria: 1. Heavy alcohol use defined as consumption of \> 20 grams daily for women or \> 30 grans daily for men for at least 3 consecutive months over the past 5 years assessed using the Lifetime Drinking History Questionnaire 2. Known diagnosis of diabetes, use of any anti-diabetic medications (including thiazolidinediones or metformin), fasting glucose \>126mg/dL, or hemoglobin A1c (HbA1c) ≥6.5%. Participants with stable use of metformin ≥6 months will be permitted if it is being used for pre-diabetes or another non-diabetes indication (e.g., PCOS). 3. Use of any specific pharmacological treatments for NAFLD/nonalcoholic steatohepatitis except vitamin E 4. Known cirrhosis, Child-Pugh score ≥7, stage 4 fibrosis on biopsy, or clinical evidence of cirrhosis or portal hypertension on imaging or exam. If a subject is not known to be cirrhotic at screen but is found to be cirrhotic based on the results of liver biopsy at baseline, this subject will be referred to a hepatologist for clinical care and will be excluded from further participation in the study. 5. Chronic systemic corticosteroid use in the ≤6 months prior to the baseline visit 6. Chronic use of Actigall, methotrexate, amiodarone, or tamoxifen 7. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis 8. Use of growth hormone or growth hormone releasing hormone within the past 6 months 9. Change in lipid lowering or anti-hypertensive regimen within 2 months of screening 10. Hemoglobin \< 10.0 g/dL or Creatinine \>1.5mg/dL 11. Active malignancy 12. For men, history of prostate cancer or evidence of prostate malignancy by prostate specific antigen (PSA) \> 5 ng/mL 13. Severe chronic illness judged by the investigator to present a contraindication to participation 14. History of hypopituitarism, head irradiation or any other condition known to affect the GH axis 15. Use of physiologic testosterone (men) or estrogen or progesterone (women) unless stable use for a year or more prior to study entry 16. Routine magnetic resonance imaging (MRI) exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip 17. Weight loss surgery within 1 year before baseline. Weight loss surgery more than 1 year prior to baseline visit is permissible as long as no active weight loss (\<10% decrease in weight over past 6 months) 18. For women, positive urine pregnancy test (hCG), trying to achieve pregnancy, or breastfeeding 19. For women able to become pregnant, unwillingness to use an acceptable form of birth control during the study. 20. Known hypersensitivity to tesamorelin or mannitol 21. Contraindication to receiving beta-blocker or nitroglycerin (which are part of the coronary angiography) 22. Significant radiation exposure, including any history of radiation therapy, or any of the following in the 12 months prior to randomization: a) more than 2 percutaneous coronary interventions; b) more than 2 myocardial perfusion studies; 3) more than 2 computed tomography angiograms 23. Active consideration for a procedure or treatment that involves significant radiation exposure as defined above in the 12 months following randomization 24. Not willing or able to adhere to dose schedules and required procedures per protocol 25. Judged by the investigator to be inappropriate for the study for other reasons not detailed above.

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