search
Back to results

Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea (ComboPlus)

Primary Purpose

Sleep Apnea

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SAS0421a
SAS0421b
SAS0421c
placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Ages 18 - 79 years
  • Suspected or diagnosed OSA

Exclusion criteria:

  • 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
    • 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

Sites / Locations

  • Brigham and Women's Hospital
  • Monash University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

SAS0421a, SAS0421b and SAS0421c

SAS0421a and SAS0421b

SAS0421c

Placebo

Arm Description

Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.

Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.

Participants will take SAS0421c for 3 days. Half doses will be given on the first night.

Participants will take placebos for 3 days.

Outcomes

Primary Outcome Measures

Apnea-hypopnea index [AHI]
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline

Secondary Outcome Measures

Hypoxic Burden
Desaturation area under curve × event frequency
Arousal Index
Number of arousals per hour (>=3-sec), % change from baseline
Visual Analog Scale for Sleep Quality
Sleep Quality 0-10 scale, 0 worst sleep quality, 10 best sleep quality
Visual Analog Scale for Waking Unrefreshed
Waking Unrefreshed 0-10 scale, 0 extremely refreshed, 10 extremely unrefreshed

Full Information

First Posted
March 26, 2019
Last Updated
February 28, 2022
Sponsor
Brigham and Women's Hospital
Collaborators
Apnimed
search

1. Study Identification

Unique Protocol Identification Number
NCT03892772
Brief Title
Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
Acronym
ComboPlus
Official Title
Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 14, 2019 (Actual)
Primary Completion Date
July 3, 2021 (Actual)
Study Completion Date
July 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Apnimed

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAS0421a, SAS0421b and SAS0421c
Arm Type
Experimental
Arm Description
Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
Arm Title
SAS0421a and SAS0421b
Arm Type
Active Comparator
Arm Description
Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
Arm Title
SAS0421c
Arm Type
Active Comparator
Arm Description
Participants will take SAS0421c for 3 days. Half doses will be given on the first night.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will take placebos for 3 days.
Intervention Type
Drug
Intervention Name(s)
SAS0421a
Intervention Description
treatment will be given for 3 days
Intervention Type
Drug
Intervention Name(s)
SAS0421b
Intervention Description
treatment will be given for 3 days
Intervention Type
Drug
Intervention Name(s)
SAS0421c
Intervention Description
treatment will be given for 3 days
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo will be given for 3 days
Primary Outcome Measure Information:
Title
Apnea-hypopnea index [AHI]
Description
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Hypoxic Burden
Description
Desaturation area under curve × event frequency
Time Frame
3 days
Title
Arousal Index
Description
Number of arousals per hour (>=3-sec), % change from baseline
Time Frame
3 days
Title
Visual Analog Scale for Sleep Quality
Description
Sleep Quality 0-10 scale, 0 worst sleep quality, 10 best sleep quality
Time Frame
3 days
Title
Visual Analog Scale for Waking Unrefreshed
Description
Waking Unrefreshed 0-10 scale, 0 extremely refreshed, 10 extremely unrefreshed
Time Frame
3 days
Other Pre-specified Outcome Measures:
Title
Visual Analog Scale for Excessive Fatigue
Description
Excessive Fatigue 0-10 scale, 0 no fatigue, 10 highly fatigued
Time Frame
3 days
Title
Visual Analog Scale for Low Energy
Description
Low Energy 0-10 scale, 0 no trouble with energy, 10 extremely low energy
Time Frame
3 days
Title
Visual Analog Scale for Treatment Satisfaction
Description
Treatment Satisfaction 0-10 scale, 0 extremely dissatisfied, 10 extremely satisfied
Time Frame
3 days
Title
Proportion of Total Sleep Time in non-REM Stage 1
Description
% Total sleep time
Time Frame
3 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Ages 18 - 79 years Suspected or diagnosed OSA Exclusion criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott A Sands, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bradley A Edwards, PhD
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Monash University
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
Immediately after publication. No end date.
IPD Sharing 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.

Learn more about this trial

Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea

We'll reach out to this number within 24 hrs