Effects of Growth Hormone Releasing Hormone in HIV - Full Text View

Purpose

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.

Condition	Intervention
HIV HIV Lipodystrophy	Drug: tesamorelin Drug: placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines HIV/AIDS Hormones

Drug Information available for: Somatropin Tesamorelin

Genetic and Rare Diseases Information Center resources: Lipodystrophy Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Liver Fat [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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).
Visceral Adipose Tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.

Secondary Outcome Measures:

Intramyocellular Lipid [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
Endogenous Growth Hormone Secretion [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given.
Insulin Sensitivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
HbA1c [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Hemoglobin A1c.
Insulin Like Growth Factor 1 (IGF-I) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Insulin Like Growth Factor 1 (IGF-I).
Lipid Panel [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Fasting lipids. Triglyceride value is given.
Carotid Intimal Medial Thickness (cIMT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Carotid Intimal Medial Thickness (cIMT).
Glucose Tolerance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.
Adiponectin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
adiponectin.
Hemostatic Markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.


Enrollment:	54
Study Start Date:	December 2010
Study Completion Date:	February 2014
Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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	Drug: tesamorelin 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 Other Name: Egrifta, growth hormone releasing hormone, TH9507
Placebo Comparator: 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	Drug: placebo 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

Eligibility


Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women age 18-65
Previously diagnosed HIV infection
Stable antiviral regimen for at least 12 weeks prior to enrollment
WC>95 cm and WHR>0.94 for male, WC>94 cm and WHR>0.88 for female occurring in the context of treatment for HIV disease
Subjective evidence of at least one of the following recent changes, occurring during the treatment of HIV disease: increased abdominal girth, relative loss of fat in the extremities, or relative loss of fat in the face
For female subjects 40yo or older, negative mammogram within one year of baseline

Exclusion Criteria:

Use of anti-diabetic agents, Megace, testosterone or any steroid use within 6 months of the study. Stable use of testosterone (> 6 mos) at dose equivalent to 200 mg IM q 2 weeks or < 10g/day to skin will be permitted.
Use of GH or GHRH within the past 6 months
Change in lipid lowering or antihypertensive regimen within 3 months of screening
Fasting blood sugar > 126 mg/dL, SGOT > 2.5 times ULN, HgB < 12.0 g/dL, creatinine > 1.4 mg/dL, CD4 count < 200
Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
For men, history of prostate cancer or evidence of prostate malignancy by PSA > 5 ng/mL
Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
For women, positive urine hCG
Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.
Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263717

Locations


United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators


Principal Investigator:	Steven Grinspoon, MD	Massachusetts General Hospital

More Information

Publications:

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.


Responsible Party:	Steven K. Grinspoon, MD, Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01263717 History of Changes
Other Study ID Numbers:	2007p-000638
Study First Received:	December 16, 2010
Results First Received:	September 8, 2014
Last Updated:	October 10, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:


HIV lipodystrophy tesamorelin Egrifta growth hormone releasing hormone

Additional relevant MeSH terms:


Lipodystrophy Lipid Metabolism Disorders Metabolic Diseases Skin Diseases Skin Diseases, Metabolic	Growth Hormone-Releasing Hormone Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Pharmacologic Actions Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 01, 2015