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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tesamorelin | Experimental | tesamorelin (brand name Egrifta) 2mg daily given subcutaneously |
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| Placebo | Placebo Comparator | identical placebo given subcutaneously daily |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tesamorelin | Drug | Tesamorelin F4 formulation 1.4mg daily |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| NAFLD Activity Score | 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. | change from baseline to 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
Final Research Data, with all patient identifiers removed, will be available to other researchers through request to the PI. Because information contained in the final research data will include multiple demographic and biological variables that could potentially be used in concert to identify participants, it will be shared only under a Data Sharing Agreement that includes (1) a commitment to using the data only for research purposes and not to identify any individual participant and (2) a commitment to destroying or returning the data after analyses are completed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tesamorelin | tesamorelin (brand name Egrifta) 2mg daily given subcutaneously Tesamorelin: Tesamorelin F4 formulation 1.4mg daily |
| FG001 | Placebo | identical placebo given subcutaneously daily Identical Placebo: Placebo injection daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| 12-month Double-blind Phase |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 25, 2023 |
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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)
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| Identical Placebo | Drug | Placebo injection daily |
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| Low Density Lipoprotein (LDL) Cholesterol |
All available data utilized. Data not available for 2 participants in tesamorelin group and 3 participants in placebo group. |
| change from baseline to 12 months |
| C-reactive Protein | All available data utilized. Data not available for 2 participants in placebo group. | change from baseline to 12 months |
| Fibrosis Score | 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. | change from baseline to 12 months |
| COMPLETED | Indicates completion of 12 month, double-blind phase and at least one assessment at 12 month visit; primary and key secondary endpoints were measured at the 12 month visit. Please note that the 6-month open-label extension was for longer-term safety rather than efficacy endpoints. Thirty participants continued into these phase, for whom safety data are reported in the adverse effects section. |
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| NOT COMPLETED |
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| 6 Month Open Label Phase |
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| ID | Title | Description |
|---|---|---|
| BG000 | Tesamorelin | tesamorelin (brand name Egrifta) 2mg daily given subcutaneously Tesamorelin: Tesamorelin F4 formulation 1.4mg daily |
| BG001 | Placebo | identical placebo given subcutaneously daily Identical Placebo: Placebo injection daily |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Median | Inter-Quartile Range | percent change in hepatic fat fraction | change from baseline to 12 months |
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| Secondary | NAFLD Activity Score | 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. | Posted | Median | Inter-Quartile Range | units on a scale | change from baseline to 12 months |
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| Secondary | Low Density Lipoprotein (LDL) Cholesterol | All available data utilized. Data not available for 2 participants in tesamorelin group and 3 participants in placebo group. | Posted | Mean | Standard Deviation | milligrams per deciliter | change from baseline to 12 months |
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| Secondary | C-reactive Protein | All available data utilized. Data not available for 2 participants in placebo group. | Posted | Mean | Standard Deviation | milligrams per liter (mg/L) | change from baseline to 12 months |
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| Secondary | Fibrosis Score | 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 | Median | Inter-Quartile Range | units on a scale | change from baseline to 12 months |
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Adverse events for the double-blind phase occurred during months 0-12 of the study (12-month double-blind phase). Adverse events for the open-label phase occurred during months 12-18 of the study (6-month open label phase that occurred at the end of the 12- month double-blind phase).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Double-blind Phase: Tesamorelin | tesamorelin (brand name Egrifta) 2mg daily given subcutaneously for first 12 months Tesamorelin: Tesamorelin F4 formulation 1.4mg daily | 0 | 26 | 2 | 26 | 22 | 26 |
| EG001 | Double-blind Phase: Placebo | identical placebo given subcutaneously daily for first 12 months Identical Placebo: Placebo injection daily | 0 | 25 | 3 | 25 | 15 | 25 |
| EG002 | Open Label Phase | all patients receiving open-label tesamorelin from months 12-18 | 0 | 30 | 0 | 30 | 16 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| rotator cuff surgery | Surgical and medical procedures | Systematic Assessment |
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| appendicitis | Gastrointestinal disorders | Systematic Assessment |
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| major depressive disorder | Psychiatric disorders | Systematic Assessment |
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| elective knee replacement | Surgical and medical procedures | Systematic Assessment |
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| liver hematoma following biopsy | Injury, poisoning and procedural complications | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Carpal Tunnel Syndrome | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Concussion | Nervous system disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Edema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| elevated gamma glutamyl transferase | Hepatobiliary disorders | Systematic Assessment |
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| Fall | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| fever | Infections and infestations | Systematic Assessment |
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| Galactorrhea | Endocrine disorders | Systematic Assessment |
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| Gastrointeritis | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Hyperglycemia | Endocrine disorders | Systematic Assessment |
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| Injection site bruising | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Injection site erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Injection site itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Injection site redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Injection site stinging | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Loose stool | Gastrointestinal disorders | Systematic Assessment |
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| Mild loss of coordination | Nervous system disorders | Systematic Assessment |
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| Motor vehicle accident | Injury, poisoning and procedural complications | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | Systematic Assessment |
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| Nocturia | Renal and urinary disorders | Systematic Assessment |
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| Infection (unspecified) | Infections and infestations | Systematic Assessment |
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| Injection site complaints, other | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pain following liver biopsy | Injury, poisoning and procedural complications | Systematic Assessment |
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| Hyperparathyroidism | Endocrine disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| renal cyst | Renal and urinary disorders | Systematic Assessment |
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| Vertebral fractures (from fall) | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Lower extremity venous thrombosis | Blood and lymphatic system disorders | Systematic Assessment |
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| Wisdom teeth extraction | Surgical and medical procedures | Systematic Assessment |
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| Urine discoloration | Renal and urinary disorders | Systematic Assessment |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Takara Stanley | Massachusetts General Hospital | 617-724-9109 | tstanley@mgh.harvard.edu |
| Jul 9, 2025 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D009765 | Obesity |
| D056128 | Obesity, Abdominal |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C479538 | tesamorelin |
| D013007 | Growth Hormone-Releasing Hormone |
| ID | Term |
|---|---|
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
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| Male |
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| Black |
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| Other |
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| Hispanic ethnicity |
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