Body Composition and Adipose Tissue in HIV Lipodystrophy: Effects of Tesamorelin Therapy
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Change in Hepatic Lipid Content
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Tesamorelin
Subjects will be treated with tesamorelin 2 mg by subcutaneous injection daily. Enrolled subjects will have 6 visits - a baseline visit before starting tesamorelin, a visit at 1 month, 3 months, 6 months, 9 months and at 1 year of tesamorelin (GHRH analogue) therapy. Blood sampling for safety labs and clinical examinations will be performed at each visit.
干预措施: Tesamorelin (Drug)
结局指标
主要结局
Change in Hepatic Lipid Content
时间窗: Baseline and 12 months
Hepatic lipid content measured by abdominal magnetic resonance imaging (MRI)
Hepatic Lipid Content
时间窗: Baseline
Hepatic lipid content (percent) will be measured by abdominal magnetic resonance imaging (MRI).
次要结局
- Change in Relative gene expression of CD68 gene(Baseline and 12 months)
- Change in Relative gene expression on TNF-alpha gene(Baseline and 12 months)
- Change in Resting Energy Expenditure (REE)(Baseline and 12 months)
- Change in Visceral Adipose Tissue (VAT) mass(Baseline and 12 months)
- Visceral Adipose Tissue (VAT) Mass(Baseline)
- Change in Relative Gene Expression of CD68 Gene(Baseline and 12 months)
- Change in Relative Gene Expression on TNF-alpha Gene(Baseline and 12 months)
研究者
Pamela U. Freda
Professor of Medicine
Columbia University