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

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT03375788
Collaborator
(none)
76
1
2
68.4
1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
76 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, double-blind, placebo controlled phase for first 12 months, followed by open-label phase for 6 months during which all participants receive active medication (tesamorelin)Randomized, double-blind, placebo controlled phase for first 12 months, followed by open-label phase for 6 months during which all participants receive active medication (tesamorelin)
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Growth Hormone Releasing Hormone Analog to Improve Nonalcoholic Fatty Liver Disease and Associated Cardiovascular Risk
Actual Study Start Date :
Jan 17, 2019
Anticipated Primary Completion Date :
Mar 31, 2024
Anticipated Study Completion Date :
Sep 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tesamorelin

tesamorelin (brand name Egrifta) 2mg daily given subcutaneously

Drug: Tesamorelin
Tesamorelin F4 formulation 1.4mg daily
Other Names:
  • Egrifta, TH9507, Growth Hormone Releasing Hormone Analog
  • Placebo Comparator: Placebo

    identical placebo given subcutaneously daily

    Drug: Identical Placebo
    Placebo injection daily

    Outcome Measures

    Primary Outcome Measures

    1. Liver Fat Content [change from baseline to 12 months]

      Liver Fat Content as measured by hydrogen-magnetic resonance spectroscopy

    Secondary Outcome Measures

    1. NAFLD Activity Score [change from baseline to 12 months]

      NAFLD Activity Score (NAS, scored between 0-8) from liver biopsy

    2. Post-prandial hepatic de novo lipogenesis [change from baseline to 12 months]

      hepatic de novo lipogenesis as measured by stable isotope methods

    3. Non-high density lipoprotein (Non-HDL) Cholesterol [change from baseline to 12 months]

    4. C-reactive protein [change from baseline to 12 months]

    5. Fibrosis Score [change from baseline to 12 months]

      fibrosis score from liver biopsy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114

    Sponsors and Collaborators

    • Massachusetts General Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Takara Stanley, Associate Professor of Pediatrics, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT03375788
    Other Study ID Numbers:
    • R01DK114144
    First Posted:
    Dec 18, 2017
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takara Stanley, Associate Professor of Pediatrics, Massachusetts General Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 12, 2022