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| Name | Class |
|---|---|
| University of Iceland | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese Patients with Obstructive Sleep Apnea | Active Comparator | 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. |
|
| Non-obese Patients with Obstructive Sleep Apnea | Active Comparator | 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. |
|
| Obese subjects without OSA | Other | Control. |
|
| Non-obese subjects without OSA | Other | Control. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Positive Airway Pressure During Sleep (ResMed S9 Elite) | Device | Positive airway pressure during sleep (ResMed S9 Elite). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change From Baseline in Sympathetic Nervous System Activity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Samuel Kuna, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34931603 | Derived | Imayama I, Gupta A, Yen PS, Chen YF, Keenan B, Townsend RR, Chirinos JA, Weaver FM, Carley DW, Kuna ST, Prasad B. Socioeconomic status impacts blood pressure response to positive airway pressure treatment. J Clin Sleep Med. 2022 May 1;18(5):1287-1295. doi: 10.5664/jcsm.9844. | |
| 33461313 | Derived | Xu L, Keenan BT, Maislin D, Gislason T, Benediktsdottir B, Gudmundsdottir S, Gardarsdottir M, Staley B, Pack FM, Guo X, Feng Y, Chahwala J, Manaktala P, Hussein A, Reddy-Koppula M, Hashmath Z, Lee J, Townsend RR, Schwab RJ, Pack AI, Kuna ST, Chirinos JA. Effect of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Cardiac Remodeling as Assessed by Cardiac Biomarker and Magnetic Resonance Imaging in Nonobese and Obese Adults. Hypertension. 2021 Mar 3;77(3):980-992. doi: 10.1161/HYPERTENSIONAHA.120.15882. Epub 2021 Jan 19. |
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The number of participants enrolled is the number of participants who agreed to participate in the study following completion of the informed consent process. The number of participants Started is the number of participants who were assigned to each Arm/Group.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
| FG001 | 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
| FG002 | Obese Subjects Without OSA | Control. Usual Care: Usual care. |
| FG003 | Non-obese Subjects Without OSA | Control. Usual Care: Usual care. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | These numbers reflect the overall number of participants who completed 4 months of CPAP treatment (i.e., the completer's analysis) and have complete data for this outcome. | Posted | Mean | Inter-Quartile Range | mm Hg | 4 months |
|
From enrollment until completion of tests and procedures
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| High blood pressure | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Samuel T. Kuna, MD | University of Pennsylvania | 215-823-4400 | skuna@mail.med.upenn.edu |
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| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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| Usual Care | Other | Usual care. |
|
Change from Baseline in Sympathetic Nervous System Activity as measured by 24-hour urine collection for norepinephrine levels.
| 4 months |
| Change From Baseline in Circulating Inflammatory Biomarker | Change from Baseline in Circulating Inflammatory Biomarker: IL-6. | 4 months |
| Change From Baseline in Oxidative Stress | Overnight urinary excretion of 8-isoprostane. | 4 months |
| 30353806 | Derived | Feng Y, Maislin D, Keenan BT, Gislason T, Arnardottir ES, Benediktsdottir B, Chirinos JA, Townsend RR, Staley B, Pack FM, Sifferman A, Pack AI, Kuna ST. Physical Activity Following Positive Airway Pressure Treatment in Adults With and Without Obesity and With Moderate-Severe Obstructive Sleep Apnea. J Clin Sleep Med. 2018 Oct 15;14(10):1705-1715. doi: 10.5664/jcsm.7378. |
| BG001 |
| 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
| BG002 | Obese Subjects Without OSA | Control. Usual Care: Usual care. |
| BG003 | Non-obese Subjects Without OSA | Control. Usual Care: Usual care. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). |
|
|
| 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. | These numbers reflect the overall number of participants who completed 4 months of CPAP treatment (i.e., the completer's analysis) and have complete data for this outcome. | Posted | Mean | Standard Deviation | lapses | 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. | These numbers reflect the overall number of participants who completed 4 months of CPAP treatment (i.e., the completer's analysis) and have complete data for this outcome. | Posted | Mean | Standard Deviation | mcg/24 hours | 4 months |
|
|
|
| Secondary | Change From Baseline in Circulating Inflammatory Biomarker | Change from Baseline in Circulating Inflammatory Biomarker: IL-6. | These numbers reflect the overall number of participants who completed 4 months of CPAP treatment (i.e., the completer's analysis) and have complete data for this outcome. | Posted | Mean | Standard Deviation | pg/mL | 4 months |
|
|
|
| Secondary | Change From Baseline in Oxidative Stress | Overnight urinary excretion of 8-isoprostane. | Data were not collected. | Posted | 4 months |
|
|
| 1 |
| 129 |
| 5 |
| 129 |
| 32 |
| 129 |
| EG001 | 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. Positive Airway Pressure During Sleep (ResMed S9 Elite): Positive airway pressure during sleep (ResMed S9 Elite). | 0 | 69 | 4 | 69 | 7 | 69 |
| EG002 | Obese Patients Without Sleep Apnea | Control Obese adults between the 40 and 65 years of age without OSA as evidenced by an apnea/hypopnea index < 15 | 0 | 12 | 0 | 12 | 3 | 12 |
| EG003 | Non-obese Patients Without Sleep Apnea | Control Non-obese adults between the 40 and 65 years of age without OSA as evidenced by an apnea/hypopnea index < 15 | 0 | 30 | 0 | 30 | 0 | 30 |
| Hospitalization | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hospitalizaiton | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hospitalization | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Hospitalization | Infections and infestations | Non-systematic Assessment |
|
| Hospitalization | Gastrointestinal disorders | Non-systematic Assessment |
|
| Claustrophobia during MRI | Psychiatric disorders | Non-systematic Assessment |
|
| Abnormal finding on MiniScid | Psychiatric disorders | Non-systematic Assessment |
|
| Abnormal MRI | Gastrointestinal disorders | Non-systematic Assessment |
|
| Abnormal spirometry | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |