Effects of Growth Hormone Releasing Hormone in HIV

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01263717
• Other study ID #: 2007p-000638
• Status: Completed
• Phase: N/A
• First received: December 16, 2010
• Last updated: September 28, 2017
• Start date: December 2010
• Est. completion date: February 2014

Study information

• Verified date: September 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV
• HIV Lipodystrophy
• Lipodystrophy

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	6 months
Primary	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	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
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.	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.	6 months
Secondary	HbA1c	Hemoglobin A1c.	6 months
Secondary	Insulin Like Growth Factor 1 (IGF-I)	Insulin Like Growth Factor 1 (IGF-I).	6 months
Secondary	Lipid Panel	Fasting lipids. Triglyceride value is given.	6 months
Secondary	Carotid Intimal Medial Thickness (cIMT)	Carotid Intimal Medial Thickness (cIMT).	6 months
Secondary	Glucose Tolerance	Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.	6 months
Secondary	Adiponectin	adiponectin.	6 months
Secondary	Hemostatic Markers	Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.	6 months