The Effects of Treating Obese and Lean Patients With Sleep Apnea

Obesity Clinical Trial

— PISA  

Official title:

Responses to CPAP Treatment in Obese and Lean Sleep Apnea Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01578031
• Other study ID #: NIH P02 HL094307-01
• Status: Completed
• Phase: N/A
• Start date: March 2009
• Est. completion date: September 2014

Study information

• Verified date: June 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obesity
• Sleep Apnea
• Sleep Apnea Syndromes

Intervention

Device:
• Positive Airway Pressure During Sleep (ResMed S9 Elite)
Positive airway pressure during sleep (ResMed S9 Elite).

Other:
• Usual Care
Usual care.

Locations

Country	Name	City	State
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	University of Iceland

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Arterial Blood Pressure	Change in mean 24-hour ambulatory blood pressure from baseline following 4-months of PAP treatment	4 months
Secondary	Change From Baseline in Psychomotor Vigilance Task	Change from Baseline in Psychomotor Vigilance Task as measured by number of lapses during 10-minute Reaction time test.	4 months
Secondary	Change From Baseline in Sympathetic Nervous System Activity	Change from Baseline in Sympathetic Nervous System Activity as measured by 24-hour urine collection for norepinephrine levels.	4 months
Secondary	Change From Baseline in Circulating Inflammatory Biomarker	Change from Baseline in Circulating Inflammatory Biomarker: IL-6.	4 months
Secondary	Change From Baseline in Oxidative Stress	Overnight urinary excretion of 8-isoprostane.	4 months