Body Composition and Adipose Tissue in HIV

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03226821

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arm

50.7

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Lipodystrophy Syndrome Growth Hormone Deficiency Body Composition	Drug: Tesamorelin	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Body Composition and Adipose Tissue in HIV Lipodystrophy: Effects of Tesamorelin Therapy

Actual Study Start Date :

Feb 7, 2018

Anticipated Primary Completion Date :

Apr 30, 2022

Anticipated Study Completion Date :

Apr 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tesamorelin Patients will be treated with tesamorelin 2 mg by subcutaneous injection daily Other Names: Egrifta

Arm

Intervention/Treatment

Experimental: 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.

Drug: Tesamorelin

Patients will be treated with tesamorelin 2 mg by subcutaneous injection daily

Other Names:

Egrifta

Outcome Measures

Primary Outcome Measures

Change in Hepatic Lipid Content [Baseline and 12 months]
Hepatic lipid content measured by abdominal magnetic resonance imaging (MRI)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 68 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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