Clinical trial NCT04575740: Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea
Official title: Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sleep Apnea
Keywords: Sleep apnea
Hypoxic burden
Arousal intensity
Post-event tachycardia
Positive airway pressure
Apnea hypopnea index
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-10-05
Enrollment: 158
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Obstructive sleep apnea (OSA) is a highly prevalent disorder with adverse neurocognitive and cardio-metabolic outcomes. Continuous positive airway pressure (CPAP) is the gold standard therapeutic option to treat airway obstructions during sleep and thus, prevent its adverse cardiovascular and neurocognitive outcomes. Previous clinical trials, however, have largely failed to show a consistent impact of CPAP on these health outcomes.

One of the main limitations of these trials may be the inadequate characterization of OSA and its acute physiological consequences. By characterizing OSA based on the "apnea-hypopnea index (AHI)", there is a potential risk of negative results.

In this trial, the investigators intend to tackle this issue, by better characterization of OSA-related physiological consequences during sleep using physiologically driven metrics to capture the burden of OSA-related hypoxemia ("hypoxic burden"), autonomic response ("heart rate burden"), and sleep fragmentation ("arousal burden").


Eligibility criteria: Inclusion criteria:

* Adults aged 21-80 years.
* Participants with a previous diagnosis of moderate to severe obstructive sleep will be eligible to enroll and attend the baseline study. Patients with a total apnea-hypopnea index greater than 15 events/hr on the baseline study will be eligible for further participation.

Exclusion criteria:

* Current treatment for obstructive sleep apnea (including CPAP, oral appliances, supplemental oxygen). Patients must be untreated prior to the baseline visit.
* Use of medications that might depress respiration (including opioids, barbiturates, benzodiazepines, and Z drugs, including zolpidem, zopiclone, eszopiclone, and zaleplon).
* Active use of non-prescription opioids (e.g., cocaine, methamphetamine)
* Uncontrolled medical problem or major organ system disease, which, in the opinion of the investigators (PI and Co-Is), would interfere with the evaluation of the subject (e.g., uncontrolled hypertension, unstable coronary heart disease, etc.).
* History of congestive heart failure, renal insufficiency, systemic neurological condition that could affect respiration.
* Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:

  * central sleep apnea (\>50% of respiratory events scored as central),
  * chronic hypoventilation/hypoxemia (awake SaO2 \< 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
* Other sleep disorders: periodic limb movements (periodic limb movement arousal index \> 10/hr), narcolepsy, or parasomnias.
* Patients unable or unwilling to use CPAP.
* Insomnia or insufficient sleep (self-reported inability to sleep \>6 hrs night).
* Pregnancy (women)

Primary outcomes:
measure: Change from baseline flow-mediated vasodilation at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline 24-hour mean systolic blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Epworth Sleepiness Scale (ESS) at 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline F2-Isoprostane/Creatinine Ratio at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Albumin/Creatinine Ratio at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Albumin without Creatinine at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Oxidized low-density lipoprotein (LDL) at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Hemoglobin A1c (HbA1c) at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Plasminogen Activator Inhibitor-1 at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Fibrinogen Antigen at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Glucose at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline high sensitivity C-Reactive Protein (hs-CRP) at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Interleukin-6 (IL-6) at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Creatinine at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Cystanin C with eGFR at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline lipid panel at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline 24-hour mean diastolic blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline 24-hour mean blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline nocturnal mean systolic blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline nocturnal mean diastolic blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline nocturnal mean blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Psychomotor Vigilance Task reaction time at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Psychomotor Vigilance Task lapses per test at 12 weeks
timeFrame: 12 weeks
measure: Change from baseline Functional Outcome of Sleep Questionnaire (FOSQ) at 12 weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Ali Azarbarzin, PhD
role: PRINCIPAL_INVESTIGATOR
References: