Sleep Apnea, ObstructivePhase 2TESSANCT02387710
Tiagabine to Enhance Slow Wave Sleep in Patients With Sleep Apnea
A Phase 2 study testing Tiagabine in people with Sleep Apnea, Obstructive, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- Tiagabine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed OSA (moderate-to-severe; apnea hypopnea index >15 events/hr)
Who cannot join
- History of seizures
Trial locations and contacts
1 site in 1 country.
United States1 site
Sleep Disorders Research Program Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Inducing Slow Wave Sleep to Treat Obstructive Sleep Apnea
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.
Read the detailed description
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:
- increases the proportion of total sleep time in slow wave sleep
- raises the non-REM arousal threshold (more negative esophageal pressure) via (1).
- is preferentially effective in patients whose OSA phenotype predicts that an increase in the arousal threshold is sufficient to resolve OSA versus those without such favorable physiology. Favorable physiology is defined here as having a low ventilatory drive at which stable breathing is theoretically feasible ("stable Vdrive" is <100% above eupneic ventilatory drive) due to any combination of a "high" upper airway muscle response, "good" passive anatomy (high Vpassive), and "low" steady-state loop gain (see Owens RL et al SLEEP 2014; Wellman A et al J Appl Physiol 2011, 2013; Eckert DJ et al 2013 AJRCCM).
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- Tiagabine, Placebo
- Keywords
- arousal threshold, phenotype, tiagabine, slow wave sleep
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiagabineDrug
Also called Gabitril
GABA reuptake inhibitor
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| Tiagabine | Active comparator | Tiagabine PO 12 mg before sleep Receives: Drug: Tiagabine |
| Placebo | Placebo comparator | Placebo PO before sleep Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 night
Secondary outcomes (2)
Slow Wave Sleep (% Total Sleep Time)
Fraction of sleep spent in stage N3
Measured: 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.
Measured: 1 night
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionJun 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea, ObstructiveStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Andrew Wellman, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02387710
- Sponsor's protocol ID
- BWH-2012P000956B
- Acronym
- TESSA
- Status last verified
- Jul 2017
- First submitted
- 9 Mar 2015
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28364504
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inducing Slow Wave Sleep to Treat Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT02387710
- Acronym / sponsor ID
- TESSA / BWH-2012P000956B
- Conditions
- Sleep Apnea, Obstructive
- Keywords
- arousal threshold, phenotype, tiagabine, slow wave sleep
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 13 Mar 2015 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- increases the proportion of total sleep time in slow wave sleep
- raises the non-REM arousal threshold (more negative esophageal pressure) via (1).
- is preferentially effective in patients whose OSA phenotype predicts that an increase in the arousal threshold is sufficient to resolve OSA versus those without such favorable physiology. Favorable physiology is defined here as having a low ventilatory drive at which stable breathing is theoretically feasible ("stable Vdrive" is <100% above eupneic ventilatory drive) due to any combination of a "high" upper airway muscle response, "good" passive anatomy (high Vpassive), and "low" steady-state loop gain (see Owens RL et al SLEEP 2014; Wellman A et al J Appl Physiol 2011, 2013; Eckert DJ et al 2013 AJRCCM).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tiagabine | Active comparator | Drug: TiagabineTiagabine PO 12 mg before sleep |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo PO before sleep |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosed OSA (moderate-to-severe; apnea hypopnea index >15 events/hr)
Key exclusion criteria (1 listed)
- History of seizures
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 |
|---|---|---|
| TiagabineAlso: GabitrilGABA reuptake inhibitor | Drug | Tiagabine |
| PlaceboPlacebo comparator | Drug | Placebo |
Primary outcome
Apnea Hypopnea Index (AHI)
Time frame: 1 night
Number of apneas + hypopneas per hour of sleep. Hypopnea criteria: reduction in 30% of baseline flow plus 3% desaturation or arousal.
2 secondary outcomes
Slow Wave Sleep (% Total Sleep Time)
Time frame: 1 night
Arousal Threshold (Esophageal Pressure Swing)
Time frame: 1 night
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28364504Taranto-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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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Tiagabine in people with Sleep Apnea, Obstructive, run by Brigham and Women's Hospital 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 1 inclusion and 1 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 15 Aug 2017. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 6 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Apnea Hypopnea Index (AHI) (time frame: 1 night). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02387710, which also lists 1 linked publication.
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 15 Aug 2017.