HIV Lipodystrophy Syndrome, Growth Hormone Deficiency, Body Composition
Conditions
Keywords
HIV Lipodystrophy, Tesamorelin, Body Composition, Visceral Adiposity
Brief summary
In this study, the investigators will examine the effect of therapy with the Growth Hormone Releasing Hormone (GHRH) analog tesamorelin on body composition in patients with HIV lipodystrophy and central adiposity. This study is a single arm prospective study of tesamorelin therapy of patients with HIV lipodystrophy. Subjects will do body composition testing, adipose tissue biopsy, metabolic rate measurements and insulin sensitivity assessment before, 6 and 12 months after daily injections of tesamorelin 2 mg by subcutaneous injection.
Detailed description
HIV lipodystrophy is increasingly recognized as a common and clinically significant long-term sequelae of HIV treatment. In the HIV lipodystrophy lipohypertrophy phenotype, visceral adipose tissue (VAT) is increased and this is associated with reduced growth hormone (GH) secretion. Mounting evidence also links this phenotype with dyslipidemia, insulin resistance, subclinical atherosclerosis and cardiovascular (CV) disease in patients with HIV disease. The etiology of HIV lipodystrophy (HIVLD) with central adiposity is unclear, but this phenotype is increasingly common with newer, less lipotoxic combination anti-retroviral therapy (cART) use. VAT and hepatic lipid accumulation, are important health concerns for HIVLD patients. This body composition pattern may contribute to the increased cardiovascular risk that has been demonstrated in patients with HIV lipodystrophy. Patients with HIVLD and central adiposity have been shown to have reduced GH secretion. Thus, a medication has been developed to augment GH secretion. This medication is tesamorelin. GH supplementation in other clinical settings has been shown to reduce visceral adiposity and may reduce hepatic lipid content.
Interventions
DRUGTesamorelin
Patients will be treated with tesamorelin 2 mg by subcutaneous injection daily
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
* HIV-infected subjects with HIV lipodystrophy (HIVLD) * Abdominal fat accumulation defined as: Waist Circumference (WC) 102 cm for men, 88 cm for women, except in subjects of East/South Asian ethnicity in whom this will be defined by WC 90 cm for men and 80 cm for women. * Weight stable for 8 weeks prior to enrollment, * CD4 count \>100 cells/mm3 * HIV RNA load \<1000 copies/mL * Fasting plasma glucose \<120 mg/dL * Stable combination anti-retroviral therapy (cART) of any regimen for ≥ 8 weeks prior to study enrollment
Exclusion criteria
* Diabetes mellitus requiring medication * History of any malignancy * Abnormal renal or liver function * Pregnancy or women of childbearing age who are not using an acceptable means of contraception * History disorder of the hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism or pituitary tumor/surgery * Head irradiation or head trauma or adrenal insufficiency * Systemic glucocorticoid use * Known hypersensitivity to tesamorelin and/or mannitol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hepatic Lipid Content | Baseline and 12 months | Hepatic lipid content measured by abdominal magnetic resonance imaging (MRI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visceral Adipose Tissue (VAT) mass | Baseline and 12 months | Visceral adipose tissue mass measured by abdominal MRI |
| Change in Relative gene expression of CD68 gene | Baseline and 12 months | Relative gene expression of CD68 gene in adipose tissue |
| Change in Relative gene expression on TNF-alpha gene | Baseline and 12 months | Relative gene expression of tumor necrosis factor (TNF)-alpha gene in adipose tissue |
| Change in Resting Energy Expenditure (REE) | Baseline and 12 months | Resting metabolic rate measured by indirect calorimetry |
Countries
United States
Outcome results
None listed