Egrifta Replacement and Sleep Disordered Breathing

NCT01788462 | Withdrawn

• 1 other identifier: NA_00074675
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Lipodystrophy

Keywords

Tesamorelin; Egrifta; HIV; Lipodystrophy; Sleep Apnea

Outcome Measures

Primary Outcomes (4)

• Changes in Sleep Apnea Severity

  Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  Subjects will be evaluated prior to initiating tesamorelin therapy (baseline)

• Changes in Sleep Apnea Severity

  Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  Subjects will be evaluated at three months

• Changes in Sleep Apnea Severity

  Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  Subjects will be evaluated at six months

• Changes in Sleep Apnea Severity

  Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  Subjects will be evaluated at one year

Secondary Outcomes (2)

• Changes in Body Composition

  baseline

• Changes in Body Composition

  12 months

Study Arms (1)

HIV and Lipodystrophy

The study population will consist of HIV patients with lipodystrophy who receive Tesamorelin (Egrifta).

Drug: Tesamorelin (Egrifta)

Interventions

Tesamorelin (Egrifta) DRUG

We will observe the effects of Tesamorelin on patients with HIV and lipodystrophy.

Also known as: Egrifta TM

HIV and Lipodystrophy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Men and women with HIV infection and central lipohypertrophy about to start tesamorelin therapy will be recruited from the Endocrinology Clinic at the Johns Hopkins Outpatient Center. Physicians and members of the clinical staff will identify eligible men and briefly introduce the study to them. Patients will be offered a phone number for the Johns Hopkins Sleep Disorders Center to call if they are interested in learning more about the research study.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Sleep Disorders Center

Baltimore, Maryland, 21224, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood

MeSH Terms

Conditions

Lipodystrophy; Sleep Apnea Syndromes

Interventions

tesamorelin

Condition Hierarchy (Ancestors)

Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Philip L Smith, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 1, 2013
• First Posted: February 11, 2013
• Study Start: May 1, 2012
• Primary Completion: January 1, 2020
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

US (1)