search
Back to results

Pharmacological Intervention for Symptomatic Snoring

Primary Purpose

Snoring

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SAS2094AH and SAS2094BH
SAS2094AL and SAS2094BL
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 Snoring

Eligibility Criteria

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

Inclusion Criteria for Enrollment

  • Age 18-79 yrs
  • Self-reported habitual snoring ("most of the time" or "all of the time" on Snoring Self-Evaluation Scale)
  • Sleep-related symptoms defined by any of the following*:

    • Visual-Analog Scale for Sleep Quality ≤7/10 ("reduced sleep quality")
    • Epworth Sleepiness Scale ≥10 ("excessive daytime sleepiness")
    • Functional Outcomes of Sleep Questionnaire <18 ("reduced sleep-related quality of life").
  • Presence of a bed-partner who is able to provide feedback to the participant on snoring (Snoring Bed-Partner Evaluation Scale)

    • The intention of these criteria is to enable participants with a broad range of possible snoring symptoms to be included. We note that the Visual-Analog Scale for Sleep Quality is, on average, approximately 7/10 in patients with sleep apnea; thus, we consider a value at or below 7 to indicate "reduced sleep quality".

Exclusion Criteria for Enrollment

  • Known obstructive sleep apnea (OSA, except "mild")
  • Current treatment for OSA or snoring (continuous positive airway pressure, oral appliances, supplemental oxygen)
  • Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
  • Use of similar medications to the study drugs.
  • 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:

    o chronic hypoventilation/hypoxemia (awake oxygen saturation < 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 to the study drugs, including:

    • clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)
    • clinically-significant liver disorders
    • clinically-significant cardiovascular conditions

      • severe hypertension (systolic blood pressure above 180 mmHg or diastolic below 110 mmHg measured at baseline)
      • cardiomyopathy (left ventricular ejection fraction, 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
    • myasthenia gravis
    • pregnancy/breast-feeding

We will not make new measurements of eGFR, LVEF or document their presence/absence for each participant.

Criteria for Randomization

After the baseline visit, the following criteria need to be met to continue participation:

  • Participants with AHI≥15 events/hr (moderate-to-severe OSA, hypopneas based on a 30% reduction in flow, accompanied by either a 3% oxygen desaturation or scored EEG-arousal) on the baseline study night, will not continue further participation after the baseline visit.
  • Participants must exhibit evidence of snoring during the baseline sleep study for further participation (mean tracheal sound intensity, Leq, exceeding 80 dB); the precise cutoff will be pilot tested in ongoing protocols (where snoring is routinely measured).

Thus, strictly, the study population will include patients with symptomatic habitual snoring, with or without mild OSA (i.e. AHI<5 and 5≤AHI<15). We note that studies in patients with moderate-to-severe OSA have already been performed (AHI>15), and further studies in this population are in progress. The inclusion of "mild OSA" will prevent a gap in the inclusion criteria for the investigation of the current intervention.

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Active H

Active L

Placebo

Arm Description

Participants will take SAS2094AL and SAS2094BH for 3 days, then SAS2094AH and SAS2094BH for 7 days.

Participants will take SAS2094AL and SAS2094BL for 10 days

Participants will take placebo for 10 days.

Outcomes

Primary Outcome Measures

Snoring intensity
mean tracheal snoring sound intensity (tracheal microphone), decibels

Secondary Outcome Measures

Snoring frequency
snoring frequency (tracheal microphone), snores per hour of total sleep time
Snoring Self-Evaluation Scale
frequency, loudness, disruption, bothersome, 5-point scales
Snoring Bed-Partner Evaluation Scale
frequency, loudness, disruption, bothersome, 5-point scales
Flow-limitation frequency
breaths per hour (nasal pressure airflow shape)
Flow-limitation severity
flow:drive ratio (nasal pressure airflow shape), %
Visual-Analog Scale for Sleep Quality
0-10 scale
Mean oxygen saturation
Percentage
Stage 1 Sleep
%Total sleep time
Arousal index
events per hour of total sleep time
Visual-Analog Scale for Treatment Satisfaction
0-10 scale
Epworth Sleepiness Scale
units on a scale
Functional Outcomes of Sleep Questionnaire
30 items, units on a scale
"Would you keep using this medication?"
Yes/No

Full Information

First Posted
October 24, 2018
Last Updated
December 10, 2019
Sponsor
Brigham and Women's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT03720353
Brief Title
Pharmacological Intervention for Symptomatic Snoring
Official Title
Pharmacological Intervention for Symptomatic Snoring
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
December 17, 2018 (Actual)
Primary Completion Date
December 10, 2019 (Actual)
Study Completion Date
December 10, 2019 (Actual)

3. Sponsor/Collaborators

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

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.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Currently, there is no pharmacological intervention capable of maintaining airway patency for the treatment of snoring and airflow limitation during sleep. Here we study the effect of pharmacological stimulation of the pharyngeal muscles on snoring severity, in a randomized quadruple-blind, crossover study.
Detailed Description
Two active interventions are being studied and compared against placebo. Participants will therefore be randomized to one of six possible sequences. Washout periods will be 1 week. Effects of interventions on outcomes will be assessed using mixed effect model analyses: we will quantify the effect of active treatment 1 (referenced to placebo), the effect of active treatment 2 (referenced to placebo), adjusting for effects of time (period number), carryover effects, and baseline values (fixed effects). Participants are considered random effects. Primary outcome is based on significance of active intervention 1 versus placebo.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Active H
Arm Type
Active Comparator
Arm Description
Participants will take SAS2094AL and SAS2094BH for 3 days, then SAS2094AH and SAS2094BH for 7 days.
Arm Title
Active L
Arm Type
Active Comparator
Arm Description
Participants will take SAS2094AL and SAS2094BL for 10 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will take placebo for 10 days.
Intervention Type
Drug
Intervention Name(s)
SAS2094AH and SAS2094BH
Intervention Description
SAS2094AH and SAS2094BH for 7 days, preceded by SAS2094AL and SAS2094BH for 3 days.
Intervention Type
Drug
Intervention Name(s)
SAS2094AL and SAS2094BL
Intervention Description
SAS2094AL and SAS2094BL for 10 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for 10 days. Capsules will mimic active treatments.
Primary Outcome Measure Information:
Title
Snoring intensity
Description
mean tracheal snoring sound intensity (tracheal microphone), decibels
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Snoring frequency
Description
snoring frequency (tracheal microphone), snores per hour of total sleep time
Time Frame
1 week
Title
Snoring Self-Evaluation Scale
Description
frequency, loudness, disruption, bothersome, 5-point scales
Time Frame
1 week
Title
Snoring Bed-Partner Evaluation Scale
Description
frequency, loudness, disruption, bothersome, 5-point scales
Time Frame
1 week
Title
Flow-limitation frequency
Description
breaths per hour (nasal pressure airflow shape)
Time Frame
1 week
Title
Flow-limitation severity
Description
flow:drive ratio (nasal pressure airflow shape), %
Time Frame
1 week
Title
Visual-Analog Scale for Sleep Quality
Description
0-10 scale
Time Frame
1 week
Title
Mean oxygen saturation
Description
Percentage
Time Frame
1 week
Title
Stage 1 Sleep
Description
%Total sleep time
Time Frame
1 week
Title
Arousal index
Description
events per hour of total sleep time
Time Frame
1 week
Title
Visual-Analog Scale for Treatment Satisfaction
Description
0-10 scale
Time Frame
1 week
Title
Epworth Sleepiness Scale
Description
units on a scale
Time Frame
1 week
Title
Functional Outcomes of Sleep Questionnaire
Description
30 items, units on a scale
Time Frame
1 week
Title
"Would you keep using this medication?"
Description
Yes/No
Time Frame
1 week
Other Pre-specified Outcome Measures:
Title
Maximum Tracheal Snoring Sound Intensity
Description
Maximum Tracheal Snoring Sound Intensity, "L1", based on 99th percentile of snoring sound intensity expressed in decibels (dB)
Time Frame
1 week
Title
Visual-Analog Scales for Excessive Fatigue
Description
0-10 scale
Time Frame
1 week
Title
Visual-Analog Scales for Wake-up Unrefreshed
Description
0-10 scale
Time Frame
1 week
Title
Visual-Analog Scales for Low Energy
Description
0-10 scale
Time Frame
1 week

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 for Enrollment Age 18-79 yrs Self-reported habitual snoring ("most of the time" or "all of the time" on Snoring Self-Evaluation Scale) Sleep-related symptoms defined by any of the following*: Visual-Analog Scale for Sleep Quality ≤7/10 ("reduced sleep quality") Epworth Sleepiness Scale ≥10 ("excessive daytime sleepiness") Functional Outcomes of Sleep Questionnaire <18 ("reduced sleep-related quality of life"). Presence of a bed-partner who is able to provide feedback to the participant on snoring (Snoring Bed-Partner Evaluation Scale) The intention of these criteria is to enable participants with a broad range of possible snoring symptoms to be included. We note that the Visual-Analog Scale for Sleep Quality is, on average, approximately 7/10 in patients with sleep apnea; thus, we consider a value at or below 7 to indicate "reduced sleep quality". Exclusion Criteria for Enrollment Known obstructive sleep apnea (OSA, except "mild") Current treatment for OSA or snoring (continuous positive airway pressure, oral appliances, supplemental oxygen) Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid). Use of similar medications to the study drugs. 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: o chronic hypoventilation/hypoxemia (awake oxygen saturation < 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 to the study drugs, including: clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2) clinically-significant liver disorders clinically-significant cardiovascular conditions severe hypertension (systolic blood pressure above 180 mmHg or diastolic below 110 mmHg measured at baseline) cardiomyopathy (left ventricular ejection fraction, 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 myasthenia gravis pregnancy/breast-feeding We will not make new measurements of eGFR, LVEF or document their presence/absence for each participant. Criteria for Randomization After the baseline visit, the following criteria need to be met to continue participation: Participants with AHI≥15 events/hr (moderate-to-severe OSA, hypopneas based on a 30% reduction in flow, accompanied by either a 3% oxygen desaturation or scored EEG-arousal) on the baseline study night, will not continue further participation after the baseline visit. Participants must exhibit evidence of snoring during the baseline sleep study for further participation (mean tracheal sound intensity, Leq, exceeding 80 dB); the precise cutoff will be pilot tested in ongoing protocols (where snoring is routinely measured). Thus, strictly, the study population will include patients with symptomatic habitual snoring, with or without mild OSA (i.e. AHI<5 and 5≤AHI<15). We note that studies in patients with moderate-to-severe OSA have already been performed (AHI>15), and further studies in this population are in progress. The inclusion of "mild OSA" will prevent a gap in the inclusion criteria for the investigation of the current intervention.
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
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Data will be owned by study Sponsor Apnimed, and may be made available per request.

Learn more about this trial

Pharmacological Intervention for Symptomatic Snoring

We'll reach out to this number within 24 hrs