Mechanisms for Individual Differences in Hypertension in Obstructive Sleep

NCT03176732 | Completed

• 2 other identifiers: 823172P01HL094307-06A1
• Study Type: observational
• Target: 155
• Locations: 2 countries
• Sites: 2

Brief Summary

Hypertension is a common consequence of obstructive sleep apnea (OSA). However, not all individuals with OSA have hypertension and there are major individual differences in blood pressure response to positive airway pressure treatment of OSA. This project is focused on determining the basis of these individual differences in blood pressure response to OSA and will evaluate the possible underlying reasons for these differences. The results will help clinicians to know whether or not to expect a reduction in blood pressure (BP) to OSA treatment in a given patient and thereby personalize patient management.

Conditions

Sleep Apnea, Obstructive; Hypertension

Keywords

Sleep Apnea; Hypertension; Positive Airway Pressure; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Nocturnal mean arterial blood pressure (nMAP)

  Measured using 24-hour ambulatory blood pressure monitoring

  Measured for 24-hours at baseline and repeated after 4 months of PAP treatment.

Secondary Outcomes (2)

• Oxidative stress

  Collected overnight at baseline and repeated after 4 months of PAP treatment.

• Sympathetic activity

  Fasting blood draw collected at baseline and repeated after 4 months of PAP treatment.

Other Outcomes (6)

• Plasma renin

  Fasting blood draw collected at baseline and repeated after 4 months of PAP treatment.

• Aldosterone

  Fasting blood draw collected at baseline and repeated after 4 months of PAP treatment.

• Oxidized LDL

  Fasting blood draw collected at baseline and repeated after 4 months of PAP treatment.

Study Arms (4)

Group 1: Normotensive

Categorized by 24-hr systolic BP (SBP): normotensive (\< 125 mm Hg) on no BP medications

Device: Positive Airway Pressure

Group 2: Controlled Hypertensive

Categorized by 24-hr systolic BP (SBP): controlled hypertensive (\< 130 mm Hg) on BP medication(s) and/or lifestyle modification

Device: Positive Airway Pressure

Group 3: Uncontrolled Hypertensive

Categorized by 24-hr systolic BP (SBP): uncontrolled hypertensive (≥ 130 mm Hg) on 0-2 BP medications

Device: Positive Airway Pressure

Group 4: Hypertensive

Categorized by 24-hr systolic BP (SBP): hypertensive (≥ 135 mm Hg) resistant to 3 or more BP medications ideally including a diuretic (resistant hypertension)

Device: Positive Airway Pressure

Interventions

Positive Airway Pressure DEVICE

Participants will use Positive Airway Pressure (PAP) treatment

Group 1: Normotensive; Group 2: Controlled Hypertensive; Group 3: Uncontrolled Hypertensive; Group 4: Hypertensive

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult subjects between the ages of 18 and 75 years of age with a diagnosis of untreated moderate to severe OSA as evidenced by an apnea/hypopnea index ≥ 15 events/hour who are about to be initiated on PAP treatment. We will make a conscious effort to recruit from all ethnic and social economic backgrounds.

You may qualify if:

• Age between 18 and 75 years
• Apnea-Hypopnea Index (AHI) ≥ 15 events/hr on diagnostic polysomnography(PSG)
• No previous history of surgical treatment of OSA, and no medical treatment of OSA within the past 6 months
• Adherence to prescribed anti-hypertensive medications as assessed by an average adherence between Visits 1-2 of at least 0.85
• Arm circumference less than 50 cm

You may not qualify if:

• Unable or unwilling to provide informed consent
• No telephone access or inability to return for follow-up
• Diagnosis of another sleep disorder in addition to OSA (e.g., periodic limb movement disorder \[greater than 5 limb movements associated with arousal/hr of sleep\], central sleep apnea \[greater than 50% of apneas are central apneas\], obesity hypoventilation syndrome, narcolepsy)
• Positive urine drug screen for any of the following: amphetamines, cocaine, opiates, barbiturates, benzodiazepines, phencyclidine (PCP), alcohol (ETOH), methadone (Visit 1)
• Requiring oxygen, bi-level positive airway pressure, or adaptive servo-ventilation for treatment of OSA
• Oxygen saturation \< 87% for a period of 2 minutes during resting wakefulness during home sleep testing (HST) or PSG (Visit 2)
• Severe and inadequately controlled arterial hypertension (SBP greater than 180 mm Hg; diastolic BP greater than 110 mm Hg on 2 of 3 spot measurements on Visit 1)
• Participants with 24-hr SBP ≥ 140 mm Hg who are not on BP medications and participants on 4 or more BP medications with a 24-hr SBP \< 135 mm Hg (Visit 2)
• A clinically unstable medical condition as defined by a change in medications in the previous month, including anti-hypertensive medications, or a new medical diagnosis in the previous 2 months (e.g., myocardial infarction, chronic heart failure, unstable angina, active infection, thyroid disease, depression or psychosis, cirrhosis, surgery, or cancer)
• Shift workers, individuals who regularly experience jet lag, or have irregular work schedules by history over the last 3 months
• Women who are pregnant or sexually active and of child-bearing age not using a form of contraceptive
• Routine consumption of \> 2 alcoholic beverages/day Excessive use of caffeine (greater than 10 cups/day)
• Inability to communicate verbally or less than a 5th grade reading level

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Iceland

Reykjavik, Iceland

Location

Biospecimen

Retention: SAMPLES WITH DNA

As a part of the research protocol, we intend to draw from each participant at baseline and following 4 months of PAP therapy. All samples will be processed according to the recommended procedures for the different analyses we intend to measure and stored at -80°C until analysis.

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Hypertension; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Samuel T Kuna, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Raymond R Townsend, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: June 6, 2017
• Primary Completion: April 30, 2022
• Study Completion: June 30, 2022
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IC (1); US (1)