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The Effects of Treating Obese and Lean Patients With Sleep Apnea (PISA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Iceland
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01578031
First received: April 11, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The investigators' overall goal is to compare the effect of CPAP treatment on intermediate cardiovascular risk measures in obese versus lean patients with obstructive sleep apnea (OSA). The overall hypothesis is that, adjusting for OSA severity and obtaining normative data from non-OSA subjects with comparable amounts of visceral adiposity, the two OSA groups will have comparable improvements in daytime sleepiness, but that the cardiovascular and metabolic improvements following CPAP therapy will be decreased in OSA patients with increased visceral adipose tissue. The investigators anticipate that, although there will be a greater absolute change in markers of sympathetic activity, inflammation and oxidative stress in obese compared to lean OSA patients following CPAP treatment, the levels will still be abnormally high in the obese patients resulting in the decreased improvements in insulin resistance, arterial blood pressure, and vascular health in obese versus lean OSA patients.


Condition Intervention
Sleep Apnea
Obesity
Device: Positive Airway Pressure During Sleep (ResMed S9 Elite)
Other: Usual Care

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Responses to CPAP Treatment in Obese and Lean Sleep Apnea Patients

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Change from Baseline in Mean Arterial Blood Pressure [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Mean 24-hour ambulatory blood pressure monitoring.


Secondary Outcome Measures:
  • Change from Baseline in Psychomotor Vigilance Task [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Reaction time test.

  • Change from Baseline in Sympathetic Nervous System Activity [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    24-hour urine collection for catecholamine levels.

  • Change from Baseline in Circulating Inflammatory Biomarkers [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Circulating IL-6, CRP, and other circulating inflammatory biomarkers.

  • Change from Baseline in Oxidative Stress [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Overnight urinary excretion of 8-isoprostane.


Estimated Enrollment: 172
Study Start Date: March 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Obese Patients with Obstructive Sleep Apnea
Obese adults between the 40 and 65 years of age with a new diagnosis of OSA as evidenced by an apnea/hypopnea index ≥ 15, ≤ 75 episodes per hour, who are naïve to CPAP use will be started on CPAP treatment.
Device: Positive Airway Pressure During Sleep (ResMed S9 Elite)
Positive airway pressure during sleep (ResMed S9 Elite).
Active Comparator: Non-obese Patients with Obstructive Sleep Apnea
Non-obese adults between the 40 and 65 years of age with a new diagnosis of OSA as evidenced by an apnea/hypopnea index ≥ 15, ≤ 75 episodes per hour, who are naïve to CPAP use will be started on CPAP treatment.
Device: Positive Airway Pressure During Sleep (ResMed S9 Elite)
Positive airway pressure during sleep (ResMed S9 Elite).
Obese subjects without OSA
Control.
Other: Usual Care
Usual care.
Non-obese subjects without OSA
Control.
Other: Usual Care
Usual care.

Detailed Description:

Obesity and obstructive sleep apnea (OSA) are independent risk factors for insulin resistance, systemic hypertension and cardiovascular disease. Both obesity and OSA are associated with increased sympathetic activity, inflammatory activity, and oxidative stress, the presumed mediators of their shared clinical consequences. Due to the conflicting results of previous intervention studies treating OSA patients with CPAP, the investigators still do not know if treatment of obese OSA patients has a substantial benefit on these risk factors. In Aim 1, to determine the effects of obesity on the response to CPAP treatment in OSA patients, the investigators will compare responses in daytime sleepiness, insulin resistance, and arterial blood pressure following CPAP treatment in obese and lean OSA patients, stratified by the amount of abdominal visceral adipose tissue, a fat depot associated with increased sympathetic activity, inflammation, and oxidative stress, and a more powerful predictor than BMI of adverse cardiovascular and metabolic outcomes. Aim 2 will determine the effect of CPAP treatment in these two patients groups on sympathetic activity, and inflammatory and oxidative stress biomarkers. The overall hypothesis is that, adjusting for OSA severity and obtaining normative data from non-OSA subjects with comparable amounts of visceral adiposity (Aim 3), the two OSA groups will have comparable improvements in daytime sleepiness, but that the cardiovascular and metabolic improvements following CPAP therapy will be decreased in OSA patients with increased visceral adipose tissue. The investigators anticipate that, although there will be a greater absolute change in markers of sympathetic activity, inflammation and oxidative stress in obese compared to lean OSA patients following CPAP treatment, the levels will still be abnormally high in the obese patients resulting in the decreased improvements in insulin resistance, arterial blood pressure, and vascular health in obese versus lean OSA patients. Relevance: Obese patients are at increased risk of developing sleep apnea. Both obesity and sleep apnea are felt to increase the risk of diabetes, hypertension, and cardiovascular disease. The proposed research will begin to determine if treating obese patients with sleep apnea helps to reduce these risks. If the beneficial effects of CPAP treatment are reduced in obese compared to lean patients with sleep apnea, then treatment of sleep apnea in obese patients needs to be combined with effective management of their obesity.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 40-65 years; Will only recruit post-menopausal women not on hormone replacement therapy to avoid the potential confounding effects of female hormones on OSA prevalence and severity, fat distribution as well as the end-points (50-60)
  • Lean subjects need to have a waist circumference score <= 107 cm in men and <= 96 cm in women.
  • Obese subjects need to have a waist circumference score > 107 cm in men and > 96 cm in women
  • For OSA volunteers, 15 ≤ AHI ≤ 75 (see Preliminary Results for justification of upper limit) on full-night in-laboratory polysomnogram within the last 6 months.
  • Stable medical history and no change in medications, including anti-hypertensive and lipid-lowering medications, in the previous 2 months
  • No regular daytime use (> 3 times/week) of sedative or hypnotic medications in the last 2 months
  • Arm circumference ≤ 50 cm (manufacturer limit for performing ambulatory BP recording)

Exclusion Criteria:

  • Unable or unwilling to provide informed consent.
  • Not satisfied with reimbursement
  • Time constraints
  • No telephone access or inability to return for follow up testing.
  • BMI > 40 kg/m2.
  • Diagnosis of another sleep disorder in addition to OSA based on PSG (e.g., periodic limb movement disorder [≥ 15 limb movements/hour of sleep with arousal], central sleep apnea [≥ 50% of apneas on diagnostic PSG are central apneas], insomnia, restless legs syndrome obesity hypoventilation syndrome, or narcolepsy).
  • Previous treatment with positive airway pressure, home oxygen therapy, tracheotomy, uvulopalatopharyngoplasty, or other surgery for OSA
  • Requiring oxygen or bi-level positive airway pressure for treatment of OSA.
  • A clinically unstable medical condition as defined by a new diagnosis or change in medical management in the previous 2 months (e.g., myocardial infarction, congestive heart failure, Cheyne-Stokes breathing, unstable angina, thyroid disease, depression or psychosis, ventricular arrhythmias, cirrhosis, surgery, or recently diagnosed cancer)
  • Positive urine toxicology screen
  • Rotating Night shift workers in situations or occupations where they regularly experience jet lag, or have irregular work schedules by history over the last 6 months.
  • Routine consumption of more than 2 alcoholic beverages per day as determined by the CAGE questionnaire (63-65).
  • Unable to perform tests due to inability to communicate verbally, inability to write and read in English; less than a 5th grade reading level; visual, hearing or cognitive impairment (e.g. previous head injury); or upper extremity motor deficit (e.g., previous stroke that prevents patient from using CPAP treatment).
  • Current illicit drug use
  • Excessive caffeine use (More than 10 caffeinated beverages per day)
  • Recent or recurring history of recreational drug use leading to tolerance or dependance.
  • Subjects with known moderate to severe renal disease will not undergo the enhanced or dynamic portion of the study.
  • Women with a positive pregnancy test will be excluded from the study.
  • Subjects who are found to have mild sleep apnea will be ineligible to participate further in the study and will paid up until that time.
  • Active infection, malignancy or chronic inflammatory disorders such as autoimmune diseases since these conditions can alter inflammatory biomarker levels.
  • No metal parts in the body as participants would not be allowed to enter the magnet during their MRI
  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: NCT01578031

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
University of Iceland
Investigators
Principal Investigator: Samuel Kuna, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01578031     History of Changes
Other Study ID Numbers: NIH P02 HL094307-01
Study First Received: April 11, 2012
Last Updated: July 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Sleep Apnea
Obesity

Additional relevant MeSH terms:
Apnea
Obesity
Sleep Apnea Syndromes
Body Weight
Dyssomnias
Nervous System Diseases
Nutrition Disorders
Overnutrition
Overweight
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory
Sleep Disorders
Sleep Disorders, Intrinsic

ClinicalTrials.gov processed this record on November 24, 2014