Clinical trial NCT03226821: Body Composition and Adipose Tissue in HIV
Official title: Body Composition and Adipose Tissue in HIV Lipodystrophy: Effects of Tesamorelin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Lipodystrophy Syndrome
Growth Hormone Deficiency
Body Composition
Keywords: HIV Lipodystrophy
Tesamorelin
Body Composition
Visceral Adiposity
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-07-24
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Hepatic Lipid Content
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Change in Visceral Adipose Tissue (VAT) mass
timeFrame: Baseline and 12 months
measure: Change in Relative gene expression of CD68 gene
timeFrame: Baseline and 12 months
measure: Change in Relative gene expression on TNF-alpha gene
timeFrame: Baseline and 12 months
measure: Change in Resting Energy Expenditure (REE)
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Neuroendocrine Unit and Pituitary Center, Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Pamela U. Freda, MD
role: PRINCIPAL_INVESTIGATOR
References: