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Pharmacological Intervention for Symptomatic Snoring

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ClinicalTrials.gov Identifier: NCT03720353
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Scott Aaron Sands, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE October 24, 2018
First Posted Date  ICMJE October 25, 2018
Last Update Posted Date January 10, 2019
Actual Study Start Date  ICMJE December 17, 2018
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
Snoring intensity [ Time Frame: 1 week ]
mean tracheal snoring sound intensity (tracheal microphone), decibels
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03720353 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • Snoring frequency [ Time Frame: 1 week ]
    snoring frequency (tracheal microphone), snores per hour of total sleep time
  • Visual-Analog Scale for Sleep Quality [ Time Frame: 1 week ]
    0-10 scale
  • Snoring Self-Evaluation Scale [ Time Frame: 1 week ]
    frequency, loudness, disruption, bothersome, 5-point scales
  • Snoring Bed-Partner Evaluation Scale [ Time Frame: 1 week ]
    frequency, loudness, disruption, bothersome, 5-point scales
  • Flow-limitation frequency [ Time Frame: 1 week ]
    breaths per hour (nasal pressure airflow shape)
  • Flow-limitation severity [ Time Frame: 1 week ]
    flow:drive ratio (nasal pressure airflow shape), %
  • Mean oxygen saturation [ Time Frame: 1 week ]
    Percentage
  • Stage 1 Sleep [ Time Frame: 1 week ]
    %Total sleep time
  • Arousal index [ Time Frame: 1 week ]
    events per hour of total sleep time
  • Visual-Analog Scale for Treatment Satisfaction [ Time Frame: 1 week ]
    0-10 scale
  • Epworth Sleepiness Scale [ Time Frame: 1 week ]
    units on a scale
  • Functional Outcomes of Sleep Questionnaire [ Time Frame: 1 week ]
    30 items, units on a scale
  • "Would you keep using this medication?" [ Time Frame: 1 week ]
    Yes/No
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 24, 2018)
  • Maximum Tracheal Snoring Sound Intensity [ Time Frame: 1 week ]
    Maximum Tracheal Snoring Sound Intensity, "L1", based on 99th percentile of snoring sound intensity expressed in decibels (dB)
  • Visual-Analog Scales for Excessive Fatigue [ Time Frame: 1 week ]
    0-10 scale
  • Visual-Analog Scales for Wake-up Unrefreshed [ Time Frame: 1 week ]
    0-10 scale
  • Visual-Analog Scales for Low Energy [ Time Frame: 1 week ]
    0-10 scale
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Pharmacological Intervention for Symptomatic Snoring
Official Title  ICMJE Pharmacological Intervention for Symptomatic Snoring
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Snoring
Intervention  ICMJE
  • Drug: SAS2094AH and SAS2094BH
    SAS2094AH and SAS2094BH for 7 days, preceded by SAS2094AL and SAS2094BH for 3 days.
  • Drug: SAS2094AL and SAS2094BL
    SAS2094AL and SAS2094BL for 10 days
  • Drug: Placebo
    Placebo for 10 days. Capsules will mimic active treatments.
Study Arms  ICMJE
  • Active Comparator: Active H
    Participants will take SAS2094AL and SAS2094BH for 3 days, then SAS2094AH and SAS2094BH for 7 days.
    Intervention: Drug: SAS2094AH and SAS2094BH
  • Active Comparator: Active L
    Participants will take SAS2094AL and SAS2094BL for 10 days
    Intervention: Drug: SAS2094AL and SAS2094BL
  • Placebo Comparator: Placebo
    Participants will take placebo for 10 days.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2019
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria for Enrollment

  • Age 21-79 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 70 dB, approximately the loudness of normal speech at 3 ft); 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Scott A Sands, PhD 8572789011 sasands@bwh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03720353
Other Study ID Numbers  ICMJE 2018P002094
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Data will be owned by study Sponsor Apnimed, and may be made available per request.
Responsible Party Scott Aaron Sands, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott A Sands, PhD Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP