Egrifta Replacement and Sleep Disordered Breathing

Withdrawn

• Conditions: Lipodystrophy
• Interventions: Drug: Tesamorelin (Egrifta)

• Registration Number: NCT01788462
• Lead Sponsor: Johns Hopkins University

Brief Summary

Sleep-disordered breathing is characterized primarily by partial or total upper airway obstruction during sleep. The most common form of sleep-disordered breathing is obstructive sleep apnea (OSA) due to recurrent collapse of the upper airway with the onset of sleep state. The major risk factors associated with the development of sleep apnea are obesity and male sex. The investigators have also found a high prevalence of OSA in HIV infected men and women, particularly among those with central lipohypertrophy, which is a common finding in HIV-infected persons receiving antiretroviral therapy. Currently, our overall hypothesis is that visceral adiposity, as seen in HIV-infected persons with central lipohypertrophy, alters both mechanical properties and compensatory neuromuscular responses leading to upper airway obstruction. Based on our most recent findings in the non-HIV population, the investigators demonstrate that obesity is associated with elevations in the upper airway load (passive Pcrit) that are counterbalanced by compensatory upper airway neural responses. Moreover, the investigators have found that female sex, peripheral adiposity, and younger age are associated with increased compensatory neuromuscular responses, while male sex, central adiposity, and older age are associated with blunted compensatory responses. The loss of the compensatory neuromuscular responses leads to obstructive sleep apnea. Among HIV-infected patients with central lipohypertrophy, tesamorelin (Egrifta), a growth hormone releasing hormone (GHRH) analogue, is approved for the reduction of visceral adipose tissue. The investigators hypothesize that tesamorelin therapy will reverse both the mechanical and neurocompensatory alterations associated with increased central obesity. In this project the investigators will determine whether tesamorelin affects sleep apnea severity and compensatory neuromuscular responses of the upper airway on sleep and breathing in men and women with HIV infection. The proposed studies are designed to elucidate the pathophysiologic basis for the development of obstructive sleep apnea in this population. The studies also provide insights into the neurohumoral regulation of upper airway function, and potentially new approaches to the treatment for sleep-disordered breathing.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2013-02-01
• Study First Submitted QC: 2013-02-08
• Study First Posted: 2013-02-11
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-02
• Last Update Posted: 2017-03-03
• Primary Completion: 2020-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Consenting adult with documented HIV-infection, ages 18 - 75 years old
2. Central lipohypertrophy as determined by a clinician
3. Not currently on Egrifta (tesamorelin) therapy.

Exclusion Criteria

1. Unstable cardiovascular disease (decompensated CHF, myocardial infarction in past 3 months, revascularization procedure in past 3 months, and unstable arrhythmias);
2. Uncontrolled hypertension (BP > 190/110);
3. Presence of cor pulmonale
4. History of end stage renal disease (on dialysis);
5. History of end stage liver disease ( e.g. jaundice, ascites, history of recurrent gastrointestinal bleeding, transjugular intrahepatic portosystemic shunt (TIPS) ;
6. Bleeding disorders or coumadin use;
7. Tracheostomy
8. Active malignancy
9. Pregnancy and/or nursing mother -

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV and Lipodystrophy	Tesamorelin (Egrifta)	The study population will consist of HIV patients with lipodystrophy who receive Tesamorelin (Egrifta).

Primary Outcome Measures

Name	Time	Method
Changes in Sleep Apnea Severity	Subjects will be evaluated at one year	Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

Secondary Outcome Measures

Name	Time	Method
Changes in Body Composition	12 months	Secondary outcomes will include the percent change in anthropometric and body composition parameters as reflected by Dual-Energy Xray Absorbtiometry measurements.

Trial Locations

Locations (1)

Johns Hopkins Sleep Disorders Center; 🇺🇸 Baltimore, Maryland, United States