Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
ComboPlus
1 other identifier
interventional
23
2 countries
2
Brief 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 arousal threshold.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jan 2019
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 14, 2019
CompletedFirst Submitted
Initial submission to the registry
March 26, 2019
CompletedFirst Posted
Study publicly available on registry
March 27, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 3, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 3, 2021
CompletedMarch 2, 2022
February 1, 2022
2.5 years
March 26, 2019
February 28, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Apnea-hypopnea index [AHI]
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
3 days
Secondary Outcomes (4)
Hypoxic Burden
3 days
Arousal Index
3 days
Visual Analog Scale for Sleep Quality
3 days
Visual Analog Scale for Waking Unrefreshed
3 days
Other Outcomes (4)
Visual Analog Scale for Excessive Fatigue
3 days
Visual Analog Scale for Low Energy
3 days
Visual Analog Scale for Treatment Satisfaction
3 days
- +1 more other outcomes
Study Arms (4)
SAS0421a, SAS0421b and SAS0421c
EXPERIMENTALParticipants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
SAS0421a and SAS0421b
ACTIVE COMPARATORParticipants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
SAS0421c
ACTIVE COMPARATORParticipants will take SAS0421c for 3 days. Half doses will be given on the first night.
Placebo
PLACEBO COMPARATORParticipants will take placebos for 3 days.
Interventions
Eligibility Criteria
You may qualify if:
- Ages 18 - 79 years
- Suspected or diagnosed OSA
You may not qualify if:
- 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.
- 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
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Brigham and Women's Hospitallead
- Apnimedcollaborator
Study Sites (2)
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Monash University
Clayton, Victoria, 3168, Australia
Related Publications (2)
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.
PMID: 39688178DERIVEDSands 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.
PMID: 38286618DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Scott A Sands, PhD
Brigham and Women's Hospital
- PRINCIPAL INVESTIGATOR
Bradley A Edwards, PhD
Monash University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor of Medicine
Study Record Dates
First Submitted
March 26, 2019
First Posted
March 27, 2019
Study Start
January 14, 2019
Primary Completion
July 3, 2021
Study Completion
July 3, 2021
Last Updated
March 2, 2022
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Immediately after publication. No end date.
- Access Criteria
- 1-page proposals should be directed to Dr. Scott Sands (sasands@bwh.harvard.edu). To gain access, requestors will be asked to sign a data use agreement.
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.