Do Endotypes Predict Response and Sequelae in OSA Patients

Phase 2

Recruiting

• Conditions: Sleep Apnea, Obstructive; Sleep; Obstructive Sleep Apnea; Sleep Apnea; Sleep Disorder
• Interventions: Drug: Eszopiclone; Other: Supplemental Oxygen; Device: Continuous Positive Airway Pressure (CPAP)

• Registration Number: NCT04875364
• Lead Sponsor: University of California, San Diego

Brief Summary

This study will investigate why some people have Obstructive Sleep Apnea (OSA) and how the underlying cause may relate to OSA manifestations (including sleepiness and high blood pressure) and response to different therapeutic approaches (ie CPAP, eszopiclone, and supplemental oxygen). Understanding why someone has OSA could affect how best to treat that individual, but may also have an impact on what problems the disease might cause.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-01
• Study First Submitted: 2021-04-27
• Study First Submitted QC: 2021-05-03
• Study First Posted: 2021-05-06
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2027-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Ages 21-65 years old
• Men and women with a physician diagnosis of OSA (or strongly suspected to have sleep apnea - * see below)
• BMI 20 - 35 kg/m2

Exclusion Criteria

• Pregnancy (current or planned)

• Nursing

• Inability to provide self-consent or complete study procedures, such as questionnaires that are only available/validated in English.

• Already on effective therapy and adherent to treatment for OSA

• Other known untreated sleep fragmenting disorder, such as periodic limb movement disorder, or narcolepsy

• Circadian rhythm disorder

• Unrevascularized coronary artery disease, angina, prior heart attack or stroke, congestive heart failure

• Uncontrolled hypertension (systolic blood pressure >160, diastolic blood pressure >95)

• Chronic lung disease requiring the use of supplemental oxygen, or with evidence of hypercapnia due to obstructive lung disease.

• Presence of tracheostomy

• Hospitalization within the past 90 days

• Prior peptic ulcer disease, esophageal varices, or gastrointestinal bleeding (< 5 years)

• Prior gastric bypass surgery

• Chronic liver disease or end-stage kidney disease

• Active cancer

• Allergy to any of the study drug

• Regular use of medications known to affect control of breathing (opioids, sedatives/hypnotics including benzodiazepines, theophylline)

• Chronically using study drug (Eszopiclone)

• Active illicit substance use

• Alcohol use of >1 standard drink/night for women or >2 standard drinks/night for men nightly alcohol use

• Active smoking or vaping within the past 6 months

• Psychiatric disease, other than controlled depression/anxiety

• Prisoners

  • Subjects who are strongly suspected to have sleep apnea will be offered an overnight home sleep apnea test (HSAT) to verify OSA diagnosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early PAP Start	Continuous Positive Airway Pressure (CPAP)	After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will be set up with a loaner CPAP for 8 weeks to initiate therapy right away.
Usual PAP Start	Supplemental Oxygen	After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will remain untreated until they are set up with their clinically prescribed CPAP (typically takes about 8 weeks).
Early PAP Start	Eszopiclone	After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will be set up with a loaner CPAP for 8 weeks to initiate therapy right away.
Early PAP Start	Supplemental Oxygen	After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will be set up with a loaner CPAP for 8 weeks to initiate therapy right away.
Usual PAP Start	Eszopiclone	After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will remain untreated until they are set up with their clinically prescribed CPAP (typically takes about 8 weeks).

Primary Outcome Measures

Name	Time	Method
Psychomotor Vigilance Test	8 weeks	A 10-minutes, computerized reaction test asking subject to press a button every time a prompt appears. Faster times indicate better reactions and higher alertness.
Endothelial Dysfunction	8 weeks	Using a device called EndoPAT for a non-invasive bloodflow measure before, during, and after 5-minutes of occlusion to one arm. Differences in EndoPAT results will be compared between treatments.

Secondary Outcome Measures

Name	Time	Method
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F)	8 weeks	A 40-item questionnaire to assesses self-reported fatigue and its impact upon daily activities and function. The score ranges from 0 to 160 with greater values indicating better quality of life.
Neurocognitive Assessment: NIH Toolbox	8 weeks	This battery yields three composite scores: overall cognitive function, crystallized cognition and fluid cognition. The two tests of "crystallized cognition" are less sensitive to acquired brain dysfunction and reflect past learning experiences (Oral Reading Recognition and Picture Vocabulary). The five tests of "fluid cognition" assess multiple cognitive domains that are vulnerable to acquired brain dysfunction (i.e., Picture Sequence Memory Task = episodic memory, Dimensional Change Card Sort Task = executive function/flexibility, Pattern Comparison Task = processing speed, Flanker Inhibitory Control and Attention Task = executive function/inhibitory control, and List Sorting Task = working memory).
Insomnia Severity Index (ISI)	8 weeks	A 7-item self-report form to assess insomnia severity. Total score categories: 0-7 = No clinically significant insomnia, 8-14 = Subthreshold insomnia, 15-21 = Clinical insomnia (moderate severity), 22-28 = Clinical insomnia (severe).
Beck Depression Index-II	8 weeks	The questionnaire assesses mental health (i.e. depression). Each of the 21 items are given weighted values corresponding to a symptom of depression and summed to give a single score. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Epworth Sleepiness Scale (ESS)	8 weeks	A self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
Pittsburgh Sleep Quality Index (PSQI)	8 weeks	A 19-item, self-rated questionnaire designed to measure sleep quality and disturbance over the past month. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality.
Richard's Campbell Sleep Questionnaire (RCSQ)	8 weeks	A five-item self-report questionnaire that is used in order to assess perceived sleep depth, sleep latency (time to fall asleep), and number of awakenings, as well as sleep efficiency and quality. Each item is scored on a visual analog scale ranging from 0 mm to 100 mm, with higher scores representing better sleep. The mean score of the five items is known as the total score and represents the overall perception of sleep.
Brief Pain Inventory (Short Form)	8 weeks	A 9 item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale with 10 being the most pain.
Systolic Blood Pressure	8 weeks	Measured at rest following standard guidelines.
Patient's Assessment of Own Function Inventory (PAOF) questionnaire	8 weeks	A subjective measure of cognitive function that asks participants to rate how often they experience difficulty in four areas: memory, language/communication, sensory-motor ability, and executive function with response options from 0 ("almost never") to 5 ("almost always").
PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity	8 weeks	A self-reported form to assess how much pain a person is feeling.
SF-36 Item Health Survey (SF-36)	8 weeks	A set of 36 generic, coherent, and easily administered quality-of-life measures. Scoring consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Diastolic Blood Pressure	8 weeks	Measured at rest following standard guidelines.
PROMIS (Patient-Reported Outcomes Measurement Information System) pain interference	8 weeks	A self-reported measure the self-reported consequences of pain on relevant aspects of a person's life and may include the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities.

Trial Locations

Locations (1)

Altman Clinical and Translational Research Institute Building; 🇺🇸 La Jolla, California, United States