Obstructive Sleep ApneaPhase 2ExPRESSIONNCT04875364
Do Endotypes Predict Response and Sequelae in OSA Patients
A Phase 2 study testing Eszopiclone, Supplemental Oxygen and Continuous Positive Airway Pressure (CPAP) in people with Obstructive Sleep Apnea and Sleep Apnea, run by University of California, San Diego at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Obstructive Sleep Apnea, Sleep Apnea, Sleep Apnea, Obstructive
- What is being tested?
- Eszopiclone, Supplemental Oxygen and Continuous Positive Airway Pressure (CPAP)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 233 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2020to 11 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Altman Clinical and Translational Research Institute Building
La Jolla, California, 92037
About this study
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.
- Being tested
- Eszopiclone, Supplemental Oxygen, Continuous Positive Airway Pressure (CPAP)
- Keywords
- sleep, sleep apnea, OSA, obstructive sleep apnea, lunesta, cpap, endotype, Eszopiclone
- Medical subject headings
- Sleep Apnea, Obstructive, Sleep Apnea Syndromes, Sleep Wake Disorders, Microcephaly, Primary Autosomal Recessive, 6
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EszopicloneDrug
Also called Lunesta
2mg of Eszopiclone just before going to sleep.
Supplemental OxygenOther
Constant oxygen flow at 4 Liters per minutes for the duration of time in bed via nasal cannula.
Continuous Positive Airway Pressure (CPAP)Device
A standard CPAP device will be provided using the settings as prescribed by the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Early PAP Start | Experimental | 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. Receives: Drug: Eszopiclone; Other: Supplemental Oxygen; Device: Continuous Positive Airway Pressure (CPAP) |
| Usual PAP Start | Experimental | 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). Receives: Drug: Eszopiclone; Other: Supplemental Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 8 weeks
Secondary outcomes (14)
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).
Measured: 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'.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 8 weeks
PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity
A self-reported form to assess how much pain a person is feeling.
Measured: 8 weeks
Systolic Blood Pressure
Measured at rest following standard guidelines.
Measured: 8 weeks
Diastolic Blood Pressure
Measured at rest following standard guidelines.
Measured: 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").
Measured: 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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start1 Aug 2020
- Primary completion11 Feb 2026
- Study completion11 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Atul Malhotra, University of California, San Diego
- Investigators
- Atul Malhotra, MD, Principal investigator, Professor, MedicineChristopher Schmickl, Principal investigator, Postdoc Fellow, Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04875364
- Sponsor's protocol ID
- 201432
- Acronym
- ExPRESSION
- Status last verified
- Jun 2026
- First submitted
- 27 Apr 2021
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Endotypes Predict Response and Sequelae in OSA Patients
- ClinicalTrials.gov ID
- NCT04875364
- Acronym / sponsor ID
- ExPRESSION / 201432
- Keywords
- sleep, sleep apnea, OSA, obstructive sleep apnea, lunesta, cpap, endotype, Eszopiclone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 233 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 11 Feb 2026 (actual)
- Study completion
- 11 Feb 2026 (actual)
- First posted
- 6 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early PAP Start | Experimental | Drug: Eszopiclone, Other: Supplemental Oxygen, Device: 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 | Experimental | Drug: Eszopiclone, Other: Supplemental OxygenAfter 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). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EszopicloneAlso: Lunesta2mg of Eszopiclone just before going to sleep. | Drug | Early PAP Start, Usual PAP Start |
| Supplemental OxygenConstant oxygen flow at 4 Liters per minutes for the duration of time in bed via nasal cannula. | Other | Early PAP Start, Usual PAP Start |
| Continuous Positive Airway Pressure (CPAP)A standard CPAP device will be provided using the settings as prescribed by the treating physician. | Device | Early PAP Start |
Primary outcome
Psychomotor Vigilance Test
Time frame: 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
Time frame: 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.
14 secondary outcomes
Neurocognitive Assessment: NIH Toolbox
Time frame: 8 weeks
Epworth Sleepiness Scale (ESS)
Time frame: 8 weeks
Pittsburgh Sleep Quality Index (PSQI)
Time frame: 8 weeks
Insomnia Severity Index (ISI)
Time frame: 8 weeks
Richard's Campbell Sleep Questionnaire (RCSQ)
Time frame: 8 weeks
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F)
Time frame: 8 weeks
Beck Depression Index-II
Time frame: 8 weeks
SF-36 Item Health Survey (SF-36)
Time frame: 8 weeks
Brief Pain Inventory (Short Form)
Time frame: 8 weeks
PROMIS (Patient-Reported Outcomes Measurement Information System) pain intensity
Time frame: 8 weeks
Systolic Blood Pressure
Time frame: 8 weeks
Diastolic Blood Pressure
Time frame: 8 weeks
Patient's Assessment of Own Function Inventory (PAOF) questionnaire
Time frame: 8 weeks
PROMIS (Patient-Reported Outcomes Measurement Information System) pain interference
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Atul Malhotra, MD principal investigator
Professor, Medicine
Christopher Schmickl principal investigator
Postdoc Fellow, Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eszopiclone, Supplemental Oxygen and Continuous Positive Airway Pressure (CPAP) in people with Obstructive Sleep Apnea and Sleep Apnea, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Psychomotor Vigilance Test (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.