Body Composition and Adipose Tissue in HIV

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

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.

Study Overview

• Status: Recruiting
• Conditions: Body Composition; Growth Hormone Deficiency; HIV Lipodystrophy Syndrome
• Intervention / Treatment: Drug: Tesamorelin

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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Carlos Reyes-Vidal, MD; Phone Number: 212-305-4921; Email: csr52@columbia.edu
• Study Contact Backup: Name: Pamela Freda, MD; Phone Number: 212-305-2254

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Neuroendocrine Unit and Pituitary Center, Columbia University
      • Contact: Pamela U. Freda, MD; Phone Number: 212-305-2254
      • Contact: Carlos M. Reyes-Vidal, MD; Phone Number: 212-305-4921; Email: csr52@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hepatic Lipid Content	Hepatic lipid content measured by abdominal magnetic resonance imaging (MRI)	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visceral Adipose Tissue (VAT) mass	Visceral adipose tissue mass measured by abdominal MRI	Baseline and 12 months
Change in Relative gene expression of CD68 gene	Relative gene expression of CD68 gene in adipose tissue	Baseline and 12 months
Change in Relative gene expression on TNF-alpha gene	Relative gene expression of tumor necrosis factor (TNF)-alpha gene in adipose tissue	Baseline and 12 months
Change in Resting Energy Expenditure (REE)	Resting metabolic rate measured by indirect calorimetry	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Pamela U. Freda, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): April 30, 2023

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Body Composition; Visceral Adiposity; HIV Lipodystrophy; Tesamorelin
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; HIV Infections; Skin Diseases, Metabolic; Lipodystrophy; HIV-Associated Lipodystrophy Syndrome; Physiological Effects of Drugs; Growth Substances; Tesamorelin
• Other Study ID Numbers: AAAR2634; R01DK110771 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No