Clinical trial NCT03720353: Pharmacological Intervention for Symptomatic Snoring
Official title: Pharmacological Intervention for Symptomatic Snoring
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Snoring
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-10-25
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Snoring intensity
timeFrame: 1 week
Secondary outcomes:
measure: Snoring frequency
timeFrame: 1 week
measure: Snoring Self-Evaluation Scale
timeFrame: 1 week
measure: Snoring Bed-Partner Evaluation Scale
timeFrame: 1 week
measure: Flow-limitation frequency
timeFrame: 1 week
measure: Flow-limitation severity
timeFrame: 1 week
measure: Visual-Analog Scale for Sleep Quality
timeFrame: 1 week
measure: Mean oxygen saturation
timeFrame: 1 week
measure: Stage 1 Sleep
timeFrame: 1 week
measure: Arousal index
timeFrame: 1 week
measure: Visual-Analog Scale for Treatment Satisfaction
timeFrame: 1 week
measure: Epworth Sleepiness Scale
timeFrame: 1 week
measure: Functional Outcomes of Sleep Questionnaire
timeFrame: 1 week
measure: "Would you keep using this medication?"
timeFrame: 1 week
Other outcomes:
measure: Maximum Tracheal Snoring Sound Intensity
timeFrame: 1 week
measure: Visual-Analog Scales for Excessive Fatigue
timeFrame: 1 week
measure: Visual-Analog Scales for Wake-up Unrefreshed
timeFrame: 1 week
measure: Visual-Analog Scales for Low Energy
timeFrame: 1 week
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Scott A Sands, PhD
role: PRINCIPAL_INVESTIGATOR
References: