Effects of Growth Hormone Releasing Hormone in HIV

Mass General Brigham

Status: Completed

Conditions: HIV Lipodystrophy; HIV

Treatments: Drug: tesamorelin; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01263717

2007p-000638

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 2 patient groups, including a placebo group

Tesamorelin

Experimental group

Description:

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

Treatment:

Drug: tesamorelin

Placebo (inactive injection)

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo