Effects of Growth Hormone Releasing Hormone in HIV

Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy

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.

Study Overview

• Status: Completed
• Conditions: HIV; HIV Lipodystrophy
• Intervention / Treatment: Drug: tesamorelin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women age 18-65
2. Previously diagnosed HIV infection
3. Stable antiviral regimen for at least 12 weeks prior to enrollment
4. 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
5. 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
6. For female subjects 40yo or older, negative mammogram within one year of baseline

Exclusion Criteria:

1. 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.
2. Use of GH or GHRH within the past 6 months
3. Change in lipid lowering or antihypertensive regimen within 3 months of screening
4. Fasting blood sugar > 126 mg/dL, SGOT > 2.5 times ULN, HgB < 12.0 g/dL, creatinine > 1.4 mg/dL, CD4 count < 200
5. Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
6. For men, history of prostate cancer or evidence of prostate malignancy by PSA > 5 ng/mL
7. Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
8. For women, positive urine hCG
9. Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.
10. Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Actual): October 30, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: HIV; lipodystrophy; tesamorelin; Egrifta; growth hormone releasing hormone
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Lipodystrophy; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Growth Substances; Hormones; Growth Hormone-Releasing Hormone; Tesamorelin
• Other Study ID Numbers: 2007p-000638