Sleep Apnea, ObstructivePhase 2DESOSANCT02436031
Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B
A Phase 2 study testing Desipramine 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. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal participants. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- Desipramine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Mar 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 65 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
- Cardiovascular disease other than well controlled hypertension
- Depression
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: The Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity During Sleep in Patients With Obstructive Sleep Apnea - Study B
Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal participants. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of desipramine (a tricyclic antidepressant with strong noradrenergic and antimuscarinic effects) on upper airway collapsibility and genioglossus muscle activity (EMG GG) during sleep in OSA patients.
Read the detailed description
Two overnight sleep studies, a placebo night and a drug night, will be performed approximately one week apart in random order. The placebo or drug will be administered 2 hours before lights out. At least 15 minutes of quiet wakefulness will be recorded to quantify the participant's EMG GG activity while awake and at sleep onset (alpha-theta transition at the electroencephalogram).
During the second part of the night, the participants will be connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and measure pharyngeal critical collapsing pressure (Pcrit), ventilation at 0 cmH2O when UA muscle are passive and active as well as change in EMG GG as a function of epiglottic pressure (muscle responsiveness).
Apnea-hypopnea index (AHI) will be calculated in each night from the part of the study off CPAP.
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- Desipramine, Placebo
- 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.
DesipramineDrug
Also called Norpramine
200 mg administered 2 hours before normal sleep time
PlaceboDrug
Placebo-matching desipramine administered 2 hours before normal sleep time
| Study group | Role | What they receive |
|---|---|---|
| Desipramine First, Placebo Second | Active comparator | Desipramine 200 mg administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching desipramine administered 2 hours before normal sleep time on second study night. Receives: Drug: Desipramine; Drug: Placebo |
| Placebo First, Desipramine Second | Experimental | Placebo-matching desipramine administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then desipramine administered 2 hours before normal sleep time on second study night. Receives: Drug: Desipramine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility
Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure. Following a baseline recording period of 5 minutes, the CPAP level was reduced to varying suboptimal pressures. Change in Pcrit was used to determine the collapsibility of the upper airway under both passive and active conditions, and is expressed as Passive Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are passive; Active Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are active. Improved=more negative Pcrit.
Measured: 1 night
Secondary outcomes (2)
Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings
Electromyography (EMG) was used to analyze genioglossus (GG) [EMG GG] muscle activity. EMG GG activity was recorded via standard needle electrodes inserted into the genioglossus muscle (tongue). Activity of EMG GG was measured during wakefulness and sleep as % of maximum activation obtained pushing the tongue against closed teeth during wakefulness (GG%max). Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure and measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness) (%max/cmH2O).
Measured: 1 night
Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep
The AHI is the number of apneas (pauses in breathing) or hypopneas (shallow breathing) recorded during the study per hour of sleep. Data for the calculation of the AHI was collected while the participant was in NREM sleep in the supine position and off CPAP (breathing spontaneously).
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 posted6 May 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2015
- Study completionMar 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.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 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
- Investigators
- Andrew Wellman, MD PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02436031
- Sponsor's protocol ID
- BWH-2014P001033B
- Acronym
- DESOSA
- Status last verified
- Feb 2017
- First submitted
- 1 May 2015
- Last updated
- 30 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity During Sleep in Patients With Obstructive Sleep Apnea - Study B
- ClinicalTrials.gov ID
- NCT02436031
- Acronym / sponsor ID
- DESOSA / BWH-2014P001033B
- Conditions
- Sleep Apnea, Obstructive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Posted 30 Mar 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. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal participants. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of desipramine (a tricyclic antidepressant with strong noradrenergic and antimuscarinic effects) on upper airway collapsibility and genioglossus muscle activity (EMG GG) during sleep in OSA patients.
Detailed description
Two overnight sleep studies, a placebo night and a drug night, will be performed approximately one week apart in random order. The placebo or drug will be administered 2 hours before lights out. At least 15 minutes of quiet wakefulness will be recorded to quantify the participant's EMG GG activity while awake and at sleep onset (alpha-theta transition at the electroencephalogram).
During the second part of the night, the participants will be connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and measure pharyngeal critical collapsing pressure (Pcrit), ventilation at 0 cmH2O when UA muscle are passive and active as well as change in EMG GG as a function of epiglottic pressure (muscle responsiveness).
Apnea-hypopnea index (AHI) will be calculated in each night from the part of the study off CPAP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Desipramine First, Placebo Second | Active comparator | Drug: Desipramine, Drug: PlaceboDesipramine 200 mg administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching desipramine administered 2 hours before normal sleep time on second study night. |
| Placebo First, Desipramine Second | Experimental | Drug: Desipramine, Drug: PlaceboPlacebo-matching desipramine administered 2 hours before normal sleep time on first study night, then a 1-week non-treatment period, then desipramine administered 2 hours before normal sleep time on second study night. |
Who may qualify
- Ages
- 18 to 65 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 (2 listed)
- Cardiovascular disease other than well controlled hypertension
- Depression
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 |
|---|---|---|
| DesipramineAlso: Norpramine200 mg administered 2 hours before normal sleep time | Drug | Desipramine First, Placebo Second, Placebo First, Desipramine Second |
| PlaceboPlacebo-matching desipramine administered 2 hours before normal sleep time | Drug | Desipramine First, Placebo Second, Placebo First, Desipramine Second |
Primary outcome
Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility
Time frame: 1 night
Participants were connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which provided a wide range of pressures between 20 and -20 cm H2O in order to modify upper airway pressure. Following a baseline recording period of 5 minutes, the CPAP level was reduced to varying suboptimal pressures. Change in Pcrit was used to determine the collapsibility of the upper airway under both passive and active conditions, and is expressed as Passive Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are passive; Active Pcrit: ventilation at a nasal pressure of 0 cm H2O when pharyngeal muscles are active. Improved=more negative Pcrit.
2 secondary outcomes
Genioglossus Muscle Responsiveness to Progressively Greater Epiglottic Pressure Swings
Time frame: 1 night
Number of Apnoea-Hypopnea Index (AHI) Events During Non-Random Eye Movement (NREM) Sleep
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 30 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Sleep Apnea, Obstructive
RecruitingObservational study
Development and Validation of a Multimodal Deep Learning Model Using Peripheral Oxygen Saturation and Ballistocardiography Signals for Predicting Apnea-Hypopnea Index in Obstructive Sleep Apnea
Obstructive Sleep Apnea
RecruitingPhase 3
A Study to Learn About the Monthly Dosing Study Medicine Called Berobenatide in Adults With Breathing Problems During Sleep and Overweight or Obesity Who Do Not Use a Breathing Machine (PAP) (VESPER-OSA 2)
Apnea, Sleep Disorders
Not yet recruitingPhase 2
Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use.
Sleep-disordered Breathing, Chronic Opioid Use
Recruiting
Nightly Wearable Monitoring During Home-Based Submental Electrical Stimulation for Obstructive Sleep Apnea
Obstructive Sleep Apnea
RecruitingPhase 1/2
DRonabinol Treatment of OSA
Obstructive Sleep Apnea
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.
Andrew Wellman, MD PhD principal investigator
Brigham and Women's Hospital
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 Desipramine 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 2 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 30 Mar 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. 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 30 Mar 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?
Change in Pharyngeal Critical Collapsing Pressure (Pcrit) as a Measure of Upper Airway Collapsibility (time frame: 1 night). 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 30 Mar 2017.