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Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. Interestingly, the severity of OSA is profoundly reduced in deep sleep (called "slow wave sleep"), potentially via an increase in the stimulus required to arouse from sleep. Here the investigators test the idea that the medication called "tiagabine" improves slow wave sleep and reduces OSA severity. The investigators will also test whether tiagabine raises the arousal threshold (more negative esophageal pressure), and whether detailed OSA "phenotyping" characteristics can predict the improvement in OSA severity with this intervention.
The current study tests the primary hypothesis that tiagabine improves sleep apnea severity in patients with moderate-to-severe sleep apnea (apnea hypopnea index measured in supine non-REM sleep; hypopneas defined by 3% desaturation or arousal). The investigators test three secondary hypotheses that tiagabine:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tiagabine | Active Comparator | Tiagabine PO 12 mg before sleep |
|
| Placebo | Placebo Comparator | Placebo PO before sleep |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tiagabine | Drug | GABA reuptake inhibitor |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Apnea Hypopnea Index (AHI) | Number of apneas + hypopneas per hour of sleep. Hypopnea criteria: reduction in 30% of baseline flow plus 3% desaturation or arousal. | 1 night |
| Measure | Description | Time Frame |
|---|---|---|
| Slow Wave Sleep (% Total Sleep Time) | Fraction of sleep spent in stage N3 | 1 night |
| Arousal Threshold (Esophageal Pressure Swing) | The arousal threshold was quantified as the mean of all the nadir negative esophageal pressure swings immediately preceding an arousal at the end of an obstructive apnea or hypopnea during both placebo and tiagabine nights. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sleep Disorders Research Program Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28364504 | Derived | Taranto-Montemurro L, Sands SA, Edwards BA, Azarbarzin A, Marques M, de Melo C, Eckert DJ, White DP, Wellman A. Effects of Tiagabine on Slow Wave Sleep and Arousal Threshold in Patients With Obstructive Sleep Apnea. Sleep. 2017 Feb 1;40(2):zsw047. doi: 10.1093/sleep/zsw047. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tiagabine First, Placebo Second | Tiagabine 12 mg administered at normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching tiagabine administered at normal sleep time on second study night. |
| FG001 | Placebo First, Tiagabine Second | Placebo-matching tiagabine administered at normal sleep timeon first study night, then a 1-week non-treatment, then tiagabine 12 mg administered at normal sleep time on second study night |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Study Night |
| |||||||||||||
| Second Study Night |
|
18 patients enrolled, 2 did not completed the study, One patient was excluded because of predominantly central sleep apnea on both nights, and another was excluded because of low-quality EEG data. Therefore, 14 subjects were analyzed.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Analyzed Participants | All patients who were randomized, completed both study nights and were included in the analysis |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Apnea Hypopnea Index (AHI) | Number of apneas + hypopneas per hour of sleep. Hypopnea criteria: reduction in 30% of baseline flow plus 3% desaturation or arousal. | Posted | Median | Inter-Quartile Range | events/hour | 1 night |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tiagabine | Tiagabine 12 mg administered at sleep time on the first or second study night |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew Wellman, MD, PhD | Brigham and women's Hospital | awellman@rics.bwh.harvard.edu |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000078308 | Tiagabine |
| ID | Term |
|---|---|
| D009557 | Nipecotic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D010880 | Piperidines |
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| Placebo | Drug | Placebo comparator |
|
| 1 night |
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Participants |
|
|
|
| Secondary | Slow Wave Sleep (% Total Sleep Time) | Fraction of sleep spent in stage N3 | Posted | Median | Inter-Quartile Range | % total sleep time | 1 night |
|
|
|
| Secondary | Arousal Threshold (Esophageal Pressure Swing) | The arousal threshold was quantified as the mean of all the nadir negative esophageal pressure swings immediately preceding an arousal at the end of an obstructive apnea or hypopnea during both placebo and tiagabine nights. | Posted | Median | Inter-Quartile Range | cmH2O | 1 night |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Placebo | Placebo administered at sleep time on the first or second study night | 0 | 14 | 0 | 14 | 0 | 14 |
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| D020919 |
| Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |