Egrifta Replacement and Sleep Disordered Breathing

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2013 by Johns Hopkins University
Sponsor:
Information provided by (Responsible Party):
Philip L. Smith ll MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01788462
First received: February 1, 2013
Last updated: February 8, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Lipodystrophy
Drug: Tesamorelin (Egrifta)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Egrifta Replacement and Sleep Disordered Breathing

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Changes in Sleep Apnea Severity [ Time Frame: Subjects will be evaluated prior to initiating tesamorelin therapy (baseline) ] [ Designated as safety issue: No ]
    Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  • Changes in Sleep Apnea Severity [ Time Frame: Subjects will be evaluated at three months ] [ Designated as safety issue: No ]
    Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  • Changes in Sleep Apnea Severity [ Time Frame: Subjects will be evaluated at six months ] [ Designated as safety issue: No ]
    Sleep apnea severity (AHI), change in sleep apnea severity (∆ AHI), and compensatory neuromuscular responses (AT/DBT, ∆ AT/DBT) will be the primary outcome variables.

  • Changes in Sleep Apnea Severity [ Time Frame: Subjects will be evaluated at one year ] [ Designated as safety issue: No ]
    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:
  • Changes in Body Composition [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Secondary outcomes will include the percent change in anthropometric and body composition parameters as reflected by Dual-Energy Xray Absorbtiometry measurements.

  • Changes in Body Composition [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Secondary outcomes will include the percent change in anthropometric and body composition parameters as reflected by Dual-Energy Xray Absorbtiometry measurements.


Biospecimen Retention:   Samples Without DNA

Blood


Estimated Enrollment: 20
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
HIV and Lipodystrophy
The study population will consist of HIV patients with lipodystrophy who receive Tesamorelin (Egrifta).
Drug: Tesamorelin (Egrifta)
We will observe the effects of Tesamorelin on patients with HIV and lipodystrophy.
Other Name: Egrifta TM

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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 -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01788462

Contacts
Contact: Michelle Guzman 410-550-6336 mguzman4@jhmi.edu
Contact: Erin Hawks 410-550-2764 ihawks@jhu.edu

Locations
United States, Maryland
Johns Hopkins Sleep Disorders Center Not yet recruiting
Baltimore, Maryland, United States, 21224
Contact: Michelle Guzman    410-550-6336    mguzman4@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Philip L Smith, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Philip L. Smith ll MD, Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01788462     History of Changes
Other Study ID Numbers: NA_00074675
Study First Received: February 1, 2013
Last Updated: February 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Tesamorelin
Egrifta
HIV
Lipodystrophy
Sleep Apnea

Additional relevant MeSH terms:
Lipodystrophy
Sleep Apnea Syndromes
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on August 21, 2014