Sleep ApneaPhase 1/2ComboPlusNCT03892772
Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
A Phase 1/2 study testing SAS0421a, SAS0421b and SAS0421c in people with Sleep Apnea, run by Brigham and Women's Hospital at 2 sites in 2 countries.
Trial summary
Currently, there is no pharmacological intervention for OSA that targets multiple pathophysiological deficits in combination. Here the investigators study the effect on sleep apnea severity of combinations of pharmacological agents that stimulate the pharyngeal muscles, stabilize ventilatory control, and increase the… Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Sleep Apnea
- What is being tested?
- SAS0421a, SAS0421b and SAS0421c
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 14 Jan 2019to 3 Jul 2021
- Phase
- Phase 1/2
- 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 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18 - 79 years
- Suspected or diagnosed OSA
Who cannot join
- Any uncontrolled medical condition
- Current use of the medications under investigation
- Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
- Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines).
- Current use of SNRIs/SSRIs or anticholinergic medications.
- Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
Show all 39Show fewer
- Respiratory disorders other than sleep disordered breathing:
- chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
- Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
- Contraindications for SAS0421a and SAS0421b, including:
- hypersensitivity to SAS0421a and SAS0421b (angioedema or urticaria)
- pheochromocytoma
- use of monoamine oxidase inhibitors
- benign prostatic hypertrophy, urinary retention
- untreated narrow angle glaucoma
- bipolar disorder, mania, psychosis
- history of major depressive disorder (age<24).
- history of attempted suicide or suicidal ideation within one year prior to screening
- clinically significant constipation, gastric retention
- pre-existing seizure disorders
- clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)
- clinically-significant liver disorders
- clinically-significant cardiovascular conditions
- severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)
- cardiomyopathy (LVEF<50%) or heart failure
- advanced atherosclerosis
- history of cerebrovascular events
- history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation
- other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
- myasthenia gravis
- pregnancy/breast-feeding
- Additional contraindications for SAS0421c, including:
- Use more than 500 mg/day of Aspirin
- Allergies to this drug class
- Adrenocortical insufficiency
- Low sodium or potassium
- hyperchloremic acidosis
- Claustrophobia
- Pregnancy or nursing
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Currently, there is no pharmacological intervention for OSA that targets multiple pathophysiological deficits in combination. Here the investigators study the effect on sleep apnea severity of combinations of pharmacological agents that stimulate the pharyngeal muscles, stabilize ventilatory control, and increase the arousal threshold.
Read the detailed description
The primary goal of the current study is to determine the effect of combination therapy targeting phenotypic traits on OSA severity. Specifically, the investigators will assess the effect of combination pharmacological therapy on OSA severity as measured by the apnea-hypopnea index and the arousal index (co-primary outcome variables).
The investigators will also estimate the effects of the interventions on the physiological traits responsible for OSA using polysomnography, namely:
- Pharyngeal anatomy and its propensity towards collapse
- The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation)
- Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep).
- Stability of the ventilatory control system feedback loop (i.e. loop gain). Baseline traits will be used to examine whether patient characteristics influence the responses to each combination of interventions (i.e. muscles, muscles plus loop gain, muscles plus arousal threshold).
- Conditions
- Sleep Apnea
- Being tested
- SAS0421a, SAS0421b, SAS0421c, placebo
- Medical subject headings
- Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAS0421aDrug
treatment will be given for 3 days
SAS0421bDrug
treatment will be given for 3 days
SAS0421cDrug
treatment will be given for 3 days
placeboDrug
placebo will be given for 3 days
| Study group | Role | What they receive |
|---|---|---|
| SAS0421a, SAS0421b and SAS0421c | Experimental | Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night. Receives: Drug: SAS0421a; Drug: SAS0421b; Drug: SAS0421c |
| SAS0421a and SAS0421b | Active comparator | Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night. Receives: Drug: SAS0421a; Drug: SAS0421b |
| SAS0421c | Active comparator | Participants will take SAS0421c for 3 days. Half doses will be given on the first night. Receives: Drug: SAS0421c |
| Placebo | Placebo comparator | Participants will take placebos for 3 days. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea-hypopnea index [AHI]
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
Measured: 3 days
Secondary outcomes (4)
Hypoxic Burden
Desaturation area under curve × event frequency
Measured: 3 days
Arousal Index
Number of arousals per hour (>=3-sec), % change from baseline
Measured: 3 days
Visual Analog Scale for Sleep Quality
Sleep Quality 0-10 scale, 0 worst sleep quality, 10 best sleep quality
Measured: 3 days
Visual Analog Scale for Waking Unrefreshed
Waking Unrefreshed 0-10 scale, 0 extremely refreshed, 10 extremely unrefreshed
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start14 Jan 2019
- Primary completion3 Jul 2021
- Study completion3 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sleep ApneaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Apnimed
- Responsible party
- Principal investigator, Scott Aaron Sands, Brigham and Women's Hospital
- Investigators
- Scott A Sands, PhD, Principal investigator, Brigham and Women's HospitalBradley A Edwards, PhD, Principal investigator, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03892772
- Sponsor's protocol ID
- 2019P000421
- Acronym
- ComboPlus
- Status last verified
- Feb 2022
- First submitted
- 26 Mar 2019
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Will IPD be available? Yes What data will be shared? All IPD collected during the study, after deidentification. When will data be available? Immediately after publication. No end date. With whom? Researchers who provide a methodologically sound proposal. For what types of analyses? Any purpose.
Publications
Hynes DJ, Mann DL, Landry SA, Joosten SA, Edwards BA, Hamilton GS. Night-to-night variability in obstructive sleep apnea severity, the physiological endotypes, and the frequency of flow limitation. Sleep. 2025 Apr 11;48(4):zsae295. doi: 10.1093/sleep/zsae295.
PubMed 39688178Sands SA, Collet J, Gell LK, Calianese N, Hess LB, Vena D, Azarbarzin A, Bertisch SM, Landry S, Thomson L, Joosten SA, Hamilton GS, Edwards BA. Combination pharmacological therapy targeting multiple mechanisms of sleep apnoea: a randomised controlled cross-over trial. Thorax. 2024 Feb 15;79(3):259-268. doi: 10.1136/thorax-2023-220184.
PubMed 38286618
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT03892772
- Acronym / sponsor ID
- ComboPlus / 2019P000421
- Conditions
- Sleep Apnea
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Apnimed
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 3 Jul 2021 (actual)
- Study completion
- 3 Jul 2021 (actual)
- First posted
- 27 Mar 2019 (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.
Currently, there is no pharmacological intervention for OSA that targets multiple pathophysiological deficits in combination. Here the investigators study the effect on sleep apnea severity of combinations of pharmacological agents that stimulate the pharyngeal muscles, stabilize ventilatory control, and increase the arousal threshold.
Detailed description
The primary goal of the current study is to determine the effect of combination therapy targeting phenotypic traits on OSA severity. Specifically, the investigators will assess the effect of combination pharmacological therapy on OSA severity as measured by the apnea-hypopnea index and the arousal index (co-primary outcome variables).
The investigators will also estimate the effects of the interventions on the physiological traits responsible for OSA using polysomnography, namely:
- Pharyngeal anatomy and its propensity towards collapse
- The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation)
- Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep).
- Stability of the ventilatory control system feedback loop (i.e. loop gain). Baseline traits will be used to examine whether patient characteristics influence the responses to each combination of interventions (i.e. muscles, muscles plus loop gain, muscles plus arousal threshold).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SAS0421a, SAS0421b and SAS0421c | Experimental | Drug: SAS0421a, Drug: SAS0421b, Drug: SAS0421cParticipants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night. |
| SAS0421a and SAS0421b | Active comparator | Drug: SAS0421a, Drug: SAS0421bParticipants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night. |
| SAS0421c | Active comparator | Drug: SAS0421cParticipants will take SAS0421c for 3 days. Half doses will be given on the first night. |
| Placebo | Placebo comparator | Drug: placeboParticipants will take placebos for 3 days. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Ages 18 - 79 years
- Suspected or diagnosed OSA
Key exclusion criteria (39 listed)
- Any uncontrolled medical condition
- Current use of the medications under investigation
- Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
- Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines).
- Current use of SNRIs/SSRIs or anticholinergic medications.
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 |
|---|---|---|
| SAS0421atreatment will be given for 3 days | Drug | SAS0421a and SAS0421b, SAS0421a, SAS0421b and SAS0421c |
| SAS0421btreatment will be given for 3 days | Drug | SAS0421a and SAS0421b, SAS0421a, SAS0421b and SAS0421c |
| SAS0421ctreatment will be given for 3 days | Drug | SAS0421a, SAS0421b and SAS0421c, SAS0421c |
| placeboplacebo will be given for 3 days | Drug | Placebo |
Primary outcome
Apnea-hypopnea index [AHI]
Time frame: 3 days
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
4 secondary outcomes
Hypoxic Burden
Time frame: 3 days
Arousal Index
Time frame: 3 days
Visual Analog Scale for Sleep Quality
Time frame: 3 days
Visual Analog Scale for Waking Unrefreshed
Time frame: 3 days
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 2 Mar 2022.
- Derived from this study: PubMed 39688178Hynes DJ, Mann DL, Landry SA, Joosten SA, Edwards BA, Hamilton GS. Night-to-night variability in obstructive sleep apnea severity, the physiological endotypes, and the frequency of flow limitation. Sleep. 2025 Apr 11;48(4):zsae295. doi: 10.1093/sleep/zsae295.
- Derived from this study: PubMed 38286618Sands SA, Collet J, Gell LK, Calianese N, Hess LB, Vena D, Azarbarzin A, Bertisch SM, Landry S, Thomson L, Joosten SA, Hamilton GS, Edwards BA. Combination pharmacological therapy targeting multiple mechanisms of sleep apnoea: a randomised controlled cross-over trial. Thorax. 2024 Feb 15;79(3):259-268. doi: 10.1136/thorax-2023-220184.
- Individual participant dataSharing planned: Yes. Will IPD be available? Yes What data will be shared? All IPD collected during the study, after deidentification. When will data be available? Immediately after publication. No end date. With whom? Researchers who provide a methodologically sound proposal. For what types of analyses? Any purpose.
Related trials for Sleep Apnea
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
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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
RecruitingObservational study
Development of a Wearable Point of Care Monitoring Device for Pediatric Obstructive Sleep Apnea
Pediatric Obstructive Sleep Apnea
RecruitingPhase 1/2
DRonabinol Treatment of OSA
Obstructive Sleep Apnea
RecruitingObservational study
Predictive Factors for Occlusal Changes in Obstructive Sleep Apnea Treatment With Mandibular Advancement Appliance
Obstructive Sleep Apnea Syndrome
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.
Scott A Sands, PhD principal investigator
Brigham and Women's Hospital
Bradley A Edwards, PhD principal investigator
Monash University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SAS0421a, SAS0421b and SAS0421c in people with Sleep Apnea, run by Brigham and Women's Hospital at 2 sites in 2 countries.
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 2 inclusion and 39 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 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Australia. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Apnea-hypopnea index [AHI] (time frame: 3 days). 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 NCT03892772, which also lists 2 linked publications.
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 2 Mar 2022; AzTrials last refreshed its copy on 6 Nov 2026.