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HIV-infection and its treatment are often associated with an increase in belly fat, as well as abnormal cholesterol and problems metabolizing sugar. People with HIV infection and increased belly fat often have decreased growth hormone (GH) levels. Low GH levels may contribute independently to increased belly fat and to increased cardiovascular risk through effects on sugar metabolism, inflammation, and other mechanisms. Tesamorelin, a growth hormone releasing hormone (GHRH) analogue, has been shown to to reduce belly fat in patients with HIV-associated abdominal fat accumulation. However, the effects of tesamorelin on fat accumulation in the liver and muscle, sugar metabolism, and cardiovascular health are not yet known. The current study is designed to determine the effects of tesamorelin treatment on fat accumulation in the muscle and liver, insulin sensitivity and sugar metabolism, and markers of cardiovascular health including blood vessel thickness (carotid intima media thickness [cIMT]) and markers of inflammation in the body. The investigators hypothesize that tesamorelin will decrease fat accumulation in the liver and muscle and will decrease markers of inflammation, with either neutral or beneficial effects on glucose metabolism.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tesamorelin | Experimental | Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose |
|
| Placebo (inactive injection) | Placebo Comparator | Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tesamorelin | Drug | Tesamorelin (growth hormone releasing hormone) 2mg daily given by subcutaneous injection x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose |
| Measure | Description | Time Frame |
|---|---|---|
| Liver Fat | Hepatic fat as measured by magnetic resonance (MR) spectroscopy, and expressed by normalizing lipid to water and expressing as a percent (lipid-to-water percent). | 6 months |
| Visceral Adipose Tissue | Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Intramyocellular Lipid | Intramyocellular lipid (IMCL) as measured by magnetic resonance (MR) spectroscopy of the calf. Soleus IMCL normalized to creatinine (IMCL/Cr based on areas determined by spectroscopy) was measured. The change over 6 months is reported. | 6 months |
| Endogenous Growth Hormone Secretion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Grinspoon, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25038357 | Result | Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):380-9. doi: 10.1001/jama.2014.8334. | |
| 29031905 | Derived | Braun LR, Feldpausch MN, Czerwonka N, Torriani M, Grinspoon SK, Stanley TL. Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation. Growth Horm IGF Res. 2017 Dec;37:1-6. doi: 10.1016/j.ghir.2017.10.002. Epub 2017 Oct 7. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tesamorelin | Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose |
| FG001 | Placebo (Inactive Injection) | Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tesamorelin | Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose |
| BG001 | Placebo (Inactive Injection) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Hepatic fat as measured by magnetic resonance (MR) spectroscopy, and expressed by normalizing lipid to water and expressing as a percent (lipid-to-water percent). | All available data were used; data were not available for some subjects. Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit. | Posted | Median | Inter-Quartile Range | Change in hepatic lipid-to-water % | 6 months |
|
6 month randomized portion of study
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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 | Tesamorelin | Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive Heart Failure | Cardiac disorders | SNOMED CT | Non-systematic Assessment | exacerbation of existing congestive heart failure |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| injection site bruising | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment |
Please note that we intended to collect and analyze data on PAI1 and tPA but we did not have sufficient funds to do this.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven K. Grinspoon, MD | Massachusetts General Hospital | 617-724-9109 | sgrinspoon@partners.org |
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| ID | Term |
|---|---|
| D008060 | Lipodystrophy |
| ID | Term |
|---|---|
| D012875 | Skin Diseases, Metabolic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D052439 | Lipid Metabolism Disorders |
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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 |
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|
| placebo | Drug | Placebo 2mg daily given by subcutaneous injection for the first 6 months of the study, followed by an open-label phase of 6 months of tesamorelin (growth hormone releasing hormone) treatment, 2mg daily given by subcutaneous injection |
|
Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given. |
| 6 months |
| Insulin Sensitivity | In a subgroup of 1/2 of the subjects, euglycemic hyperinsulinemic clamp will be performed to assess insulin-stimulated glucose uptake. Insulin stimulated glucose uptake (M) calculated using the method of DeFronzo is shown. | 6 months |
| HbA1c | Hemoglobin A1c. | 6 months |
| Insulin Like Growth Factor 1 (IGF-I) | Insulin Like Growth Factor 1 (IGF-I). | 6 months |
| Lipid Panel | Fasting lipids. Triglyceride value is given. | 6 months |
| Carotid Intimal Medial Thickness (cIMT) | Carotid Intimal Medial Thickness (cIMT). | 6 months |
| Glucose Tolerance | Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given. | 6 months |
| Adiponectin | adiponectin. | 6 months |
| Hemostatic Markers | Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum. | 6 months |
Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase |
|
|
| Primary | Visceral Adipose Tissue | Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra. | Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit. | Posted | Mean | 95% Confidence Interval | change in cm^2 after 6 months | 6 months |
|
|
|
| Secondary | Intramyocellular Lipid | Intramyocellular lipid (IMCL) as measured by magnetic resonance (MR) spectroscopy of the calf. Soleus IMCL normalized to creatinine (IMCL/Cr based on areas determined by spectroscopy) was measured. The change over 6 months is reported. | All available data were used; data were not available for some subjects. Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit. | Posted | Median | Inter-Quartile Range | Change in ratio of IMCL/Cr | 6 months |
|
|
|
| Secondary | Endogenous Growth Hormone Secretion | Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given. | All available data were used; data were not available for some subjects. | Posted | Median | Inter-Quartile Range | Change in ng/mL | 6 months |
|
|
|
| Secondary | Insulin Sensitivity | In a subgroup of 1/2 of the subjects, euglycemic hyperinsulinemic clamp will be performed to assess insulin-stimulated glucose uptake. Insulin stimulated glucose uptake (M) calculated using the method of DeFronzo is shown. | All available data were used; data were not available for some subjects. | Posted | Mean | 95% Confidence Interval | Change in mg/kg/min | 6 months |
|
|
|
| Secondary | HbA1c | Hemoglobin A1c. | All available data were used; data were not available for one subject. | Posted | Mean | 95% Confidence Interval | Change in % | 6 months |
|
|
|
| Secondary | Insulin Like Growth Factor 1 (IGF-I) | Insulin Like Growth Factor 1 (IGF-I). | All available data were used; data were not available for one subject. | Posted | Mean | Standard Deviation | Change in ng/mL | 6 months |
|
|
|
| Secondary | Lipid Panel | Fasting lipids. Triglyceride value is given. | All available data were used; data were not available for one subject. | Posted | Median | Inter-Quartile Range | Change in triglyceride, mg/dL | 6 months |
|
|
|
| Secondary | Carotid Intimal Medial Thickness (cIMT) | Carotid Intimal Medial Thickness (cIMT). | All available data were used. | Posted | Mean | 95% Confidence Interval | Change in mm | 6 months |
|
|
|
| Secondary | Glucose Tolerance | Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given. | All available data were used; data were not available for some subjects. | Posted | Mean | 95% Confidence Interval | Change in 2-hour glucose, mg/dL | 6 months |
|
|
|
| Secondary | Adiponectin | adiponectin. | All available data were used. Data were not available for 1 subject. | Posted | Median | Inter-Quartile Range | Change in ng/mL | 6 months |
|
|
|
| Secondary | Hemostatic Markers | Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum. | Please note that we do not have data for these markers (neither PAI1 or tPA) because we did not have adequate funds to assess these. | Posted | 6 months |
|
|
| 3 |
| 28 |
| 25 |
| 28 |
| EG001 | Placebo (Inactive Injection) | Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase | 3 | 22 | 21 | 22 |
|
| pneumonia | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Non-systematic Assessment | pneumonia requiring hospitalization |
|
| basal cell carcinoma | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment | diagnoses of basal cell carcinoma in 2 patients, both of whom had history of basal cell carcinoma in past |
|
| esophageal myotomy | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment | Planned Heller myotomy requiring post-procedure hospitalization |
|
| cerebrovascular accident | Vascular disorders | SNOMED CT | Non-systematic Assessment | acute cerebrovascular accident |
|
| paresthesia | Nervous system disorders | SNOMED CT | Non-systematic Assessment |
|
| erythema at injection site | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment |
|
| joint pain | Musculoskeletal and connective tissue disorders | SNOMED CT | Non-systematic Assessment | arthralgia |
|
| stinging of skin | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment | stinging at injection site |
|
| muscle pain | Musculoskeletal and connective tissue disorders | SNOMED CT | Non-systematic Assessment | myalgia |
|
| hyperglycemia | Endocrine disorders | SNOMED CT | Non-systematic Assessment |
|
| edema | Blood and lymphatic system disorders | SNOMED CT | Non-systematic Assessment |
|
| sinusitis | Infections and infestations | SNOMED CT | Non-systematic Assessment |
|
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |