The Effect of Eszopiclone on the Arousal Threshold in Sleep Apnea Syndrome

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01102270
• Collaborator: Sunovion (Industry), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 15.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether taking eszopiclone (Lunesta) changes the breathing effort required to briefly wake people with obstructive sleep apnea from sleep (respiratory arousal threshold). We would like to see if taking eszopiclone can reduce the severity of obstructive sleep apnea in some people (those that have a low respiratory arousal threshold; i.e. wake up easily to respiratory stimuli).

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Drug: Eszopiclone; Drug: Placebo	Early Phase 1

Detailed Description

Obstructive sleep apnea is an exceedingly common disease with major neurocognitive and cardiovascular consequences. The current primary treatment e.g. Continuous positive airway pressure (CPAP) is effective but poorly tolerated by many patients particularly those with mild-moderate disease. Secondary treatments such as oral appliances to advance the mandible or surgical procedures to enlarge the airway are commonly appealing to the patient. However, these approaches have only modest success in reducing apnea frequency to an acceptable level. Thus, finding tolerable and effective therapy for sleep apnea remains an important objective.

The causes of sleep apnea vary between patients. Targeted therapy according to the underlying causes of sleep apnea in individual patients is likely to be most effective. However, current therapeutic options for sleep apnea are quite limited. The purpose of this physiological research study is to determine if taking eszopiclone (Lunesta)changes the breathing effort required to briefly wake people with obstructive sleep apnea from sleep (the arousal threshold) and if administration of the sedative medication eszopiclone (Lunesta) to certain sleep apnea patients (those with a low arousal threshold ie wake up easily) would be beneficial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Double-Blind Randomized Physiological Study Examining the Effects of Eszopiclone on the Arousal Threshold and Obstructive Sleep Apnea Severity
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Eszopiclone Eszopiclone 3mg prior to sleep (1 night)	Drug: Eszopiclone; 3mg tablet once prior to sleep; Other Names: Lunesta
Placebo Comparator: Sugar Pill Sugar Pill (placebo) prior to sleep (1 night)	Drug: Placebo; 1 placebo capsule prior to sleep; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Apnea Hypopnea Index [8 hour In-Laboratory Polysomnogram (PSG)]

   number of respiratory events per hour of sleep Respiratory events last for at least 10 seconds and are associated with a decrease in blood oxygenation or a cortical arosual from sleep. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe

Secondary Outcome Measures

1. Arousal Threshold [8 hour In-Laboratory Polysomnogram (PSG)]

   quantified using an epiglottic pressure transducer in CmH2O

2. Nadir Overnight Oxygen Saturation [8 hour In-Laboratory Polysomnogram (PSG)]

   Nadir overnight oxygen saturation (%)

3. Sleep Duration [8 hour In-Laboratory Polysomnogram (PSG)]

   total sleep duration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18-64 years old

• Untreated obstructive sleep apnea

Exclusion Criteria:

• Nadir SaO2 <70% on a baseline PSG

• Medications known to affect either sleep, breathing or muscle activity

• Major co-morbidities apart from sleep apnea

• Allergy to lidocaine, oxymetazoline HCl, or eszopiclone

• Women who are pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital, Division of Sleep Medicine	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• Sunovion
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Atul Malhotra, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Atul Malhotra, MD, Associate Professor, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01102270
• Other Study ID Numbers: 2008P000818; 1P01HL095491-01
• First Posted: Apr 13, 2010
• Last Update Posted: Apr 18, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Atul Malhotra, MD, Associate Professor, Brigham and Women's Hospital: Obstructive sleep apnea; Arousal threshold; Sedative medication; upper airway
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Eszopiclone

Study Results

Participant Flow

Recruitment Details	subjects recruited 2008-2010 from clinics and ads

Arm/Group Title	Eszopiclone First, Then Sugar Pill	Sugar Pill First, Then Eszopiclone
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep followed by sugar pill (placebo) 1 week later	Placebo : 1 placebo capsule prior to sleep then 3mg eszopiclone 1 week later
Period Title: Overall Study
STARTED	8	9
COMPLETED	8	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	all study participants who received all interventions
Overall Participants	17
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (15)
Sex: Female, Male (Count of Participants)
Female	7 41.2%
Male	10 58.8%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Secondary Outcome

Title	Arousal Threshold
Description	quantified using an epiglottic pressure transducer in CmH2O
Time Frame	8 hour In-Laboratory Polysomnogram (PSG)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Sugar Pill
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep	Placebo : 1 placebo capsule prior to sleep
Measure Participants	17	17
Median (Inter-Quartile Range) [cmH2O]	-18	-14

2. Secondary Outcome

Title	Nadir Overnight Oxygen Saturation
Description	Nadir overnight oxygen saturation (%)
Time Frame	8 hour In-Laboratory Polysomnogram (PSG)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Sugar Pill
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep	Placebo : 1 placebo capsule prior to sleep
Measure Participants	17	17
Mean (Standard Error) [% oxygen saturation]	80 (1)	80 (1)

3. Primary Outcome

Title	Apnea Hypopnea Index
Description	number of respiratory events per hour of sleep Respiratory events last for at least 10 seconds and are associated with a decrease in blood oxygenation or a cortical arosual from sleep. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe
Time Frame	8 hour In-Laboratory Polysomnogram (PSG)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Sugar Pill
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep	Placebo : 1 placebo capsule prior to sleep
Measure Participants	17	17
Mean (Standard Error) [events per hour of sleep]	24 (4)	31 (5)

4. Secondary Outcome

Title	Sleep Duration
Description	total sleep duration
Time Frame	8 hour In-Laboratory Polysomnogram (PSG)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Sugar Pill
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep	Placebo : 1 placebo capsule prior to sleep
Measure Participants	17	17
Mean (Standard Error) [hours of sleep]	6.8 (0.2)	5.4 (0.4)

Adverse Events

Time Frame	Overnight study and the following morning
Arm/Group Title	Eszopiclone		Sugar Pill
Arm/Group Description	Eszopiclone : 3mg tablet once prior to sleep		Placebo : 1 placebo capsule prior to sleep
All Cause Mortality
	Eszopiclone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Eszopiclone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Eszopiclone		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)

Limitations/Caveats

We excluded patients with blood arterial oxygen saturations <70% as we wanted to avoid any potential risks associated with this group.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.