Pharmacological Intervention for Symptomatic Snoring

Snoring Clinical Trial

Official title:

Pharmacological Intervention for Symptomatic Snoring

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03720353
• Other study ID #: 2018P002094
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 17, 2018
• Est. completion date: December 10, 2019

Study information

• Verified date: December 2019
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 10, 2019
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Snoring

Intervention

Drug:
• SAS2094AH and SAS2094BH
SAS2094AH and SAS2094BH for 7 days, preceded by SAS2094AL and SAS2094BH for 3 days.
• SAS2094AL and SAS2094BL
SAS2094AL and SAS2094BL for 10 days
• Placebo
Placebo for 10 days. Capsules will mimic active treatments.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Tracheal Snoring Sound Intensity	Maximum Tracheal Snoring Sound Intensity, "L1", based on 99th percentile of snoring sound intensity expressed in decibels (dB)	1 week
Other	Visual-Analog Scales for Excessive Fatigue	0-10 scale	1 week
Other	Visual-Analog Scales for Wake-up Unrefreshed	0-10 scale	1 week
Other	Visual-Analog Scales for Low Energy	0-10 scale	1 week
Primary	Snoring intensity	mean tracheal snoring sound intensity (tracheal microphone), decibels	1 week
Secondary	Snoring frequency	snoring frequency (tracheal microphone), snores per hour of total sleep time	1 week
Secondary	Snoring Self-Evaluation Scale	frequency, loudness, disruption, bothersome, 5-point scales	1 week
Secondary	Snoring Bed-Partner Evaluation Scale	frequency, loudness, disruption, bothersome, 5-point scales	1 week
Secondary	Flow-limitation frequency	breaths per hour (nasal pressure airflow shape)	1 week
Secondary	Flow-limitation severity	flow:drive ratio (nasal pressure airflow shape), %	1 week
Secondary	Visual-Analog Scale for Sleep Quality	0-10 scale	1 week
Secondary	Mean oxygen saturation	Percentage	1 week
Secondary	Stage 1 Sleep	%Total sleep time	1 week
Secondary	Arousal index	events per hour of total sleep time	1 week
Secondary	Visual-Analog Scale for Treatment Satisfaction	0-10 scale	1 week
Secondary	Epworth Sleepiness Scale	units on a scale	1 week
Secondary	Functional Outcomes of Sleep Questionnaire	30 items, units on a scale	1 week
Secondary	"Would you keep using this medication?"	Yes/No	1 week