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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03375788

Enrollment

Registered

2017-12-18

Start date

2019-01-17

Completion date

2025-01-10

Last updated

2025-11-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

tesamorelin, obesity, fatty liver

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.

Interventions

DRUGTesamorelin

Tesamorelin F4 formulation 1.4mg daily

DRUGIdentical Placebo

Placebo injection daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

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)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Liver Fat Content	change from baseline to 12 months	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

Measure	Time frame	Description
Low Density Lipoprotein (LDL) Cholesterol	change from baseline to 12 months	All available data utilized. Data not available for 2 participants in tesamorelin group and 3 participants in placebo group.
C-reactive Protein	change from baseline to 12 months	All available data utilized. Data not available for 2 participants in placebo group.
NAFLD Activity Score	change from baseline to 12 months	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.
Fibrosis Score	change from baseline to 12 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Tesamorelin tesamorelin (brand name Egrifta) 2mg daily given subcutaneously Tesamorelin: Tesamorelin F4 formulation 1.4mg daily	26
Placebo identical placebo given subcutaneously daily Identical Placebo: Placebo injection daily	25
Total	51

Baseline characteristics

Characteristic	Tesamorelin	Placebo	Total
Age, Continuous	47 years STANDARD_DEVIATION 10	47 years STANDARD_DEVIATION 11	47 years STANDARD_DEVIATION 11
Race/Ethnicity, Customized Black	2 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized Hispanic ethnicity	1 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized Other	0 Participants	7 Participants	7 Participants
Race/Ethnicity, Customized White	23 Participants	15 Participants	38 Participants
Region of Enrollment United States	26 participants	25 participants	51 participants
Sex: Female, Male Female	12 Participants	11 Participants	23 Participants
Sex: Female, Male Male	14 Participants	14 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 26	0 / 25	0 / 30
other Total, other adverse events	22 / 26	15 / 25	16 / 30
serious Total, serious adverse events	2 / 26	3 / 25	0 / 30

Outcome results

Primary

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.