Clinical trial NCT04712656: Effects of CPAP Therapy on Blood Pressure and Heart Rate Variability in Obstructive Sleep Apnea
Official title: Effects of CPAP Therapy on Blood Pressure and Heart Rate Variability in Obstructive Sleep Apnea: Role of Symptom Subtypes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sleep Apnea, Obstructive
Keywords: Cardiovascular
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: Chang Gung Memorial Hospital
name: University of Sydney
name: The University of Western Australia
name: Peking University
name: Ruijin Hospital
name: National University of Singapore
name: University of Iceland
name: Geisinger Health
name: Charite University, Berlin, Germany
First posted: 2021-01-15
Enrollment: 1739
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adults between the ages of 30 to 75 years old with moderate to severe obstructive sleep apnea (OSA). OSA diagnosis will be defined as an apnea/hypopnea index (AHI) \>or =5 episodes per hour.

Brief summary: The primary objective of this study is to determine whether the effect of continuous positive airway pressure (CPAP) therapy on 24-hour mean blood pressure (BP) in patients with obstructive sleep apnea (OSA) varies between symptom phenotypes.

Detailed description: This is a prospective, non-randomized, multi-center, cohort study involving patients with moderate to severe OSA. This study will compare OSA patients who accept and comply with CPAP therapy versus those who do not.

Variables of Interest: 24-hour ambulatory BP, sitting BP, electrocardiogram (ECG), facial photographs, psychomotor vigilance test (PVT), questionnaires, and blood samples.

Patients will complete questionnaires that pertain to demographics, lifestyle factors, and co-morbidities associated with CVD. The blood samples will be used to look for evidence of diabetes; elevated lipids; markers of heart injury, inflammation, and coagulation; and genetic information. Measurements will be collected at baseline and at 6-month follow-up.

In addition, patients enrolled in this study will be contacted by telephone once a year over a ten year period. The purpose of the telephone interview is to determine if they are using any treatment for OSA, if they have developed any new health problems such as a heart attack or stroke, and if they have changed any of their usual medications.

Data Analysis Approach: To correct for potential bias in the non-randomized comparison, we will apply a Propensity Score (PS) Design via subclassification. Models to derive the PS values used in this design will include a number of covariates relevant to CPAP adherence and cardiovascular outcomes, including age, sex, obesity (BMI, neck circumference, waist-to-hip ratio), current smoking, prevalent CVD at baseline, history of hypertension, HbA1c, diabetes mellitus (history, medications), lipid profile, hyperlipidemia (history, medications), family history of premature coronary disease, Charlson comorbidity index, physical activity (IPAQ), diet, OSA severity (AHI, ODI4, T90), sleepiness (Epworth Sleepiness Scale), educational attainment, socioeconomic status (postcode), insomnia symptoms (Insomnia Symptom Questionnaire), anxiety and depression-related symptoms (Patient Health Questionnaire-2), self-efficacy (General self-efficacy scale), and medication adherence (Medication Adherence Report Scale \[MARS-5\]). Baseline values of outcome measures will also be included in the PS model. After creating the PS design, all analyses are performed accounting for PS subclass as a categorical stratification factor. Evaluations of the CPAP effect on binary outcomes are performed utilizing conditional logistic regression. Similarly, CPAP effects in the context of survival analyses (e.g., Cox Proportional Hazards models) or on continuous outcomes (e.g., linear regression) are assessed by including PS subclass as a categorical covariate in all models.

Eligibility criteria: Inclusion Criteria:

* 30 to 75 years of age
* Among patients with hypertension, no change in BP medication for at least 3 months.
* Willing and able to give informed consent
* Willing and able to complete ambulatory blood pressure monitoring at baseline and after 6-months.
* Sleep study \[Polysomnography (PSG) or Home Sleep Apnea Study (HSAT) performed based on clinical grounds
* 4% oxygen desaturation index (ODI4) ≥15 events/hour on clinical sleep study
* Planned CPAP treatment by treating provider

Exclusion Criteria:

* Unable to apply BP cuff (e.g. arm circumference \>55 cm, prior breast cancer, structural abnormalities of the arm)
* Current use of CPAP or Dental Device for OSA
* Category III-IV of heart failure
* Presence of Cheyne-Stokes Respiration (CSR) in PSG
* Predominantly central sleep apnea (AHI≥15 events/hour)
* Pregnancy
* History of renal failure, or renal transplant
* Self-reported sleep duration less than 5 hours per night on weeknights (work nights)
* Other sleep disorders
* Use of supplemental oxygen during wakefulness or sleep
* Self-reported illicit drug use or marijuana use more than once per week
* Unstable medical conditions: uncontrolled angina, uncontrolled hypertension, severe chronic obstructive pulmonary disease, active cancer, or unstable psychiatric disease
* Any underlying condition that, in the opinion of the lead investigator, prohibits participation in the study
* Development or adoption of any of the above exclusion criteria during the study period

Primary outcomes:
measure: 24-hour Mean Blood Pressure
timeFrame: Measurements will be conducted at baseline (prior to CPAP therapy) and 6-months after initiation of CPAP therapy.
Secondary outcomes:
measure: Heart Rate Variability
timeFrame: Measurements will be conducted at baseline (prior to CPAP therapy) and 6-months after initiation of CPAP therapy.
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Martha Morehouse Medical Pavilion, Suite 2600
state: Ohio
Study officials:
affiliation: Ohio State University
name: Ulysses Magalang, MD
role: PRINCIPAL_INVESTIGATOR
References: