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

NCT03375788 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: R01DK114144
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Fatty Liver Disease; Obesity; Obesity, Abdominal; Liver Fat; Fatty Liver

Keywords

tesamorelin; obesity; fatty liver

Outcome Measures

Primary Outcomes (1)

• Liver Fat Content

  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.

  change from baseline to 12 months

Secondary Outcomes (4)

• NAFLD Activity Score

  change from baseline to 12 months

• Low Density Lipoprotein (LDL) Cholesterol

  change from baseline to 12 months

• C-reactive Protein

  change from baseline to 12 months

• Fibrosis Score

  change from baseline to 12 months

Study Arms (2)

Tesamorelin

EXPERIMENTAL

tesamorelin (brand name Egrifta) 2mg daily given subcutaneously

Drug: Tesamorelin

Placebo

PLACEBO COMPARATOR

identical placebo given subcutaneously daily

Drug: Identical Placebo

Interventions

Tesamorelin DRUG

Tesamorelin F4 formulation 1.4mg daily

Also known as: Egrifta, TH9507, Growth Hormone Releasing Hormone Analog

Tesamorelin

Identical Placebo DRUG

Placebo injection daily

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 18-65yo
• Body mass index (BMI) ≥ 30kg/m2, or, for participants with known steatohepatitis, BMI ≥ 25kg/m2
• 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)
• 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.
• For females ≥50yo, negative mammogram within 1 year of baseline
• If use of vitamin E ≥400 international units daily, stable dose for ≥6 mos
• 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.)

You may not qualify if:

• 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
• 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).
• Use of any specific pharmacological treatments for NAFLD/nonalcoholic steatohepatitis except vitamin E
• 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.
• Chronic systemic corticosteroid use in the ≤6 months prior to the baseline visit
• Chronic use of Actigall, methotrexate, amiodarone, or tamoxifen
• Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis
• Use of growth hormone or growth hormone releasing hormone within the past 6 months
• Change in lipid lowering or anti-hypertensive regimen within 2 months of screening
• Hemoglobin \< 10.0 g/dL or Creatinine \>1.5mg/dL
• Active malignancy
• For men, history of prostate cancer or evidence of prostate malignancy by prostate specific antigen (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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity; Obesity, Abdominal; Fatty Liver

Interventions

tesamorelin; Growth Hormone-Releasing Hormone

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Limitations and Caveats

Interpretation of changes in biopsy data are limited by relatively small sample size as well as the requirement for steatosis but not steatohepatitis at baseline. In other words, not all participants had steatohepatitis or fibrosis at baseline.

Results Point of Contact

• Title: Dr. Takara Stanley
• Organization: Massachusetts General Hospital

tstanley@mgh.harvard.edu

617-724-9109

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 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)

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 18, 2017
• Study Start: January 17, 2019
• Primary Completion: July 10, 2024
• Study Completion: January 10, 2025
• Last Updated: November 20, 2025
• Results First Posted: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (1)