Do Endotypes Predict Response and Sequelae in OSA Patients (ExPRESSION)

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.

Study Overview

• Status: Recruiting
• Conditions: Sleep Apnea, Obstructive; Sleep Disorder; Sleep; Obstructive Sleep Apnea; Sleep Apnea
• Intervention / Treatment: Drug: Eszopiclone; Other: Supplemental Oxygen; Device: Continuous Positive Airway Pressure (CPAP)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pamela DeYoung; Phone Number: 8582462154; Email: pdeyoung@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Altman Clinical and Translational Research Institute Building
      • Contact: Dillon Gilbertson, MS; Phone Number: 8582462154; Email: dcgilbertson@health.ucsd.edu
      • Contact: Pamela DeYoung; Phone Number: 8582462154; Email: pdeyoung@health.ucsd.edu
      • Contact: Christopher Schmickl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early PAP Start; 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.	Drug: Eszopiclone; 2mg of Eszopiclone just before going to sleep.; Other Names: Lunesta; Other: Supplemental Oxygen; Constant oxygen flow at 4 Liters per minutes for the duration of time in bed via nasal cannula.; Device: Continuous Positive Airway Pressure (CPAP); A standard CPAP device will be provided using the settings as prescribed by the treating physician.
Experimental: Usual PAP Start; 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).	Drug: Eszopiclone; 2mg of Eszopiclone just before going to sleep.; Other Names: Lunesta; Other: Supplemental Oxygen; Constant oxygen flow at 4 Liters per minutes for the duration of time in bed via nasal cannula.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychomotor Vigilance Test	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.	8 weeks
Endothelial Dysfunction	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive Assessment: NIH Toolbox	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).	8 weeks
Epworth Sleepiness Scale (ESS)	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'.	8 weeks
Pittsburgh Sleep Quality Index (PSQI)	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.	8 weeks
Insomnia Severity Index (ISI)	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).	8 weeks
Richard's Campbell Sleep Questionnaire (RCSQ)	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.	8 weeks
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F)	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.	8 weeks
Beck Depression Index-II	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.	8 weeks
SF-36 Item Health Survey (SF-36)	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.	8 weeks
Brief Pain Inventory (Short Form)	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.	8 weeks
PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity	A self-reported form to assess how much pain a person is feeling.	8 weeks
Systolic Blood Pressure	Measured at rest following standard guidelines.	8 weeks
Diastolic Blood Pressure	Measured at rest following standard guidelines.	8 weeks
Patient's Assessment of Own Function Inventory (PAOF) questionnaire	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").	8 weeks
PROMIS (Patient-Reported Outcomes Measurement Information System) pain interference	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.	8 weeks

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Atul Malhotra, MD, Professor, Medicine; Principal Investigator: Christopher Schmickl, Postdoc Fellow, Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: sleep; OSA; obstructive sleep apnea; sleep apnea; Eszopiclone; cpap; endotype; lunesta
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Neurologic Manifestations; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleep Wake Disorders; Apnea; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: 201432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes