To Characterize the Performance of the Nasal Dilator Strip in Lowering Nasal Resistance During Sleep, Promoting Nasal Route Breathing and Reducing the Signs and Symptoms of Sleep Disordered Breathing in a Group of Chronic Nocturnal Nasal Congestion Sufferers Who Report Trouble With Their Sleep.

Study Overview
=================
Brief Summary
-----------------
To characterize the performance of the nasal dilator strip in lowering nasal resistance during sleep, promoting nasal route breathing and reducing the signs and symptoms of sleep disordered breathing in a group of chronic nocturnal nasal congestion sufferers who report trouble with their sleep.

Detailed Description
-----------------
This study was a baseline-controlled study. This study consisted of three phases: Baseline phase, 28 days Active phase (1 month in home treatment usage period with sleep laboratory nights after 7 (Night 8) and 28 days (Night 29) of treatment) followed by a two-night cross-over Nasal resistance phase. Screened participants were evaluated for sleep disordered breathing and PSG variables with sleep laboratory nights at Baseline, after 7 and 28 days of in house use of nasal dilator strip (Night 8 and 29 of Active phase), and at Day 30 and 31 (Night 30 and 31 of Nasal resistance phase). Participants wore the Nasal dilator strip during Active phase. Participants then entered the Nasal resistance phase of the study, which consisted of two sleep laboratory nights at Day 30 and 31 (Night 30 and 31) where they were randomized to receive a sequence of either 'strip'/' no strip' or 'no strip'/'strip as per there randomization schedule.

Official Title
-----------------
An Exploratory Study of a Nasal Dilator Strip

Conditions
-----------------
Sleep Disordered Breathing, Congestion, Nasal

Intervention / Treatment
-----------------
* Device: Prototype nasal dilator strip
* Other: No strip


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Nostril types I and II (Inter-axial angle below 41 degrees = type I; inter-axial angle from 41 to 70 degrees = type II) Nasal Congestion: Have chronic nocturnal nasal congestion ('always or almost always') for at least the last year. Sleep: Reports trouble with sleep Exclusion Criteria: Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to latex. Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds), allergy or atopic reaction to adhesive bandages or latex. Subject has a chronic skin condition or eczema on the face or nose. Subject has visible open sores, sunburn, irritation on the face or nose immediately prior to treatment. Subject has severe obstructive sleep apnea/hypopnea syndrome with an AHI score <30 events/hour at the Baseline visit. Subject has had a diagnosis of another major sleep disorder (i.e. primary insomnia, i.e. regularly sleeping less than 6 hours per night, sleep insufficiency, i.e. sleeping >2 hours more on non-work days as compared to work days, narcolepsy, or periodic limb movement disorder). Subject has a non-typical sleep schedule (e.g. shift-work). Subject plans travel involving time-zone changes during the study period. Subject takes medication known to have a significant effect on sleep. Use of any substance with psychotropic effects or properties known to affect sleep/wake, including but not limited to: neuroleptics, morphine/opioid derivatives, sedative antihistamines, stimulants, antidepressants, clonidine, barbiturates, anxiolytics, thalidomide, hypnotics and sedatives. Use of over the counter sleep promoting agents including diphenhydramine, doxylamine, tryptophan, valerian root, kava kava, melatonin, St John's Wort and Alluna. Use of over the counter alertness aids including caffeine and guarana. Subject currently uses any topical nasal decongestants (nasal sprays, drops, etc). Subject must have discontinued use of topical decongestants at least 7 days prior Baseline. Subject is experiencing an acute upper respiratory tract infection at during qualification phase and at Baseline visit. Subject abuses alcohol (regularly drinks more than 3 drinks per day) or has a recent history (within last 2 years) of substance or alcohol abuse. Regular consumption of xanthine-containing beverages (i.e. tea, coffee, or cola) comprising usually more than 5 cups or glasses per day. Subject has a positive drug of abuse screening result. Subject has severe, unstable disease states (e.g. myocardial infarction, congestive heart failure, diabetes, cirrhosis, cancer, epilepsy, or stroke), pain syndromes, (e.g. fibromyalgia) or any medical or surgical condition that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study or who in the judgement of the principal investigator would not be suitable for entry into this study. Severe nasal obstruction caused by structural abnormality that renders the subject unsuitable for the study in the opinion of the investigator, i.e. nasal polyps, severe deviated septum. Subject is unwilling to be videotaped or recorded during the PSG studies. Current Treatment for Sleep Disordered Breathing a) Subject currently uses devices prescribed for sleep disordered breathing including Continuous Positive Airway Pressure (CPAP), mandibular advancement devices, tongue displacement devices. b)Over-the-counter products such as chin straps, pillows, internal/external nasal dilators are acceptable provided usage is discontinued at least 28 days prior to Baseline.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study consisted of 3 phases baseline and active phase in which participants used the nasal dilator strip followed by 2 nights cross over nasal resistance phase in which participants were randomized to receive a sequence of strip/no strip or no strip/strip.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All participants (Baseline phase)<br>All the participants were applied nasal dilator strip during the sleep laboratory night on Day 1. | Device: Prototype nasal dilator strip<br>* External Prototype Nasal Dilator strip. GSK prototype nasal dilator AB 2R11. All the participants used nasal dilator strip throughout the active phase of the study (Day 1 to Day 28). Followed by that all the participants used the nasal strip on Day 29 or 30 in Nasal resistance phase of the study as per their randomization sequence.<br>|
| Experimental: All Participants (Active Phase)<br>All the participants wore nasal dilator strip over a 1 month in-home use period and returned for sleep laboratory nights after 7 (Day 8) and 28 days (Day 29) of treatment | Device: Prototype nasal dilator strip<br>* External Prototype Nasal Dilator strip. GSK prototype nasal dilator AB 2R11. All the participants used nasal dilator strip throughout the active phase of the study (Day 1 to Day 28). Followed by that all the participants used the nasal strip on Day 29 or 30 in Nasal resistance phase of the study as per their randomization sequence.<br>|
| Experimental: All Participants (Nasal Resistance Phase)<br>The participants were randomized to receive a sequence of either 'strip'/' no strip' or 'no strip'/'strip' on 2 sleep laboratory nights (on Day 30 and Day 31) based on the randomization schedule | Device: Prototype nasal dilator strip<br>* External Prototype Nasal Dilator strip. GSK prototype nasal dilator AB 2R11. All the participants used nasal dilator strip throughout the active phase of the study (Day 1 to Day 28). Followed by that all the participants used the nasal strip on Day 29 or 30 in Nasal resistance phase of the study as per their randomization sequence.<br>Other: No strip<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Resistance in Sleeping State : Nasal Resistance Phase | Nasal resistance of the participants with and without strip was measured in sleeping state using a nasal mask and a flow meter to obtain a trans-nasal pressure difference and nasal flow by continuous recording over the 2 nights [on Day 30 (Visit 5) and Day 31 (Visit 6), cumulatively], of the nasal resistance phase. | upto 2 days | 
| Area at Minimum Cross Sectional Area 1 (MCA1) : Baseline Phase | Minimum cross sectional area 1 (MCA1) in the first 3 cm of the nasal cavity behind the nostril (0-3 cm), considered to be the area of the nasal valve and the distance from the nares of this restriction. MCA 1 was measured with an Acoustic Rhinometer at Day 1 (baseline phase) before and after Nasal dilator strip application. | Day 1 | 
| Volume at Minimum Cross-sectional Area 1 (MCA1) : Baseline Phase | Volume of the first 3 cm of the nasal cavity behind the nostril (0-3 cm2). Volume at MCA1 was measured with an Acoustic Rhinometer at Day 1 before and after Nasal dilator strip application. | Day 1 | 
| Nasal Resistance by Posterior Rhinomanometry : Baseline Phase | Nasal resistance was measured on Day 1, by a modified method of posterior rhinomanometry in awake and seated position. Using posterior rhinomanometry, the transnasal pressure difference was measured between the nasopharynx and the external nares. The technique measures the difference in transnasal pressure that drives the flow of air through the nasal cavities. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Score of Composite Functional Outcomes of Sleep Questionnaire (FOSQ) : Active Phase | The FOSQ was 30-item, validated psychometric instrument that assessed the impact of disorders of excessive sleepiness on functional outcomes relevant to daily behaviors and quality of life (QoL). The responses to the questionnaire were grouped according to five factors for analysis: 1) Activity Level, 2) Vigilance, 3) Intimacy and Sexual Relationships, 4) General Productivity and 5) Social Outcome. Participant used a scale of 0 to 4 to score each question of FOSQ which then grouped in above factors (where 0= I don't do this activity for other reasons, 1= Yes, extreme difficulty, 2= Yes, moderate difficulty, 3= Yes, a little difficulty, and 4= No difficulty). Total score of composite FOSQ was the sum of scores obtained on all 30 questions of the questionnaire. The possible range for the total score of composite FOSQ was from 0-120. A higher total score of composite FOSQ indicates better QoL of the participant. | Day 29 | 
| Global Self Assessment Score : Active Phase | On Day 29, prior to sleep, participants were asked to rate their overall experience with the strip as compared to before they enrolled in the study: ease of breathing, staying asleep, falling back to sleep, waking up too early, number of awakenings, falling asleep, sleep quality, sleep depth, dry mouth upon awakening, morning headache, nocturia (waking up to urinate), feeling refreshed in the morning. Experience was rated on scale of -2 to 2 were: -2 = Much worse, -1 = Somewhat worse, 0 = No change, 1 = Somewhat improve, 2 = Much improved (higher score indicated improvement). | Day 29 | 
| Total Epworth Sleepiness Scale Score (ESS) : Active Phase | Participants answered the following question How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? 1. Sitting and reading, 2. Watching TV, 3. Sitting, inactive in a public place (e.g. a theatre or a meeting), 4. As a passenger in a car for an hour without a break, 5. Lying down to rest in the afternoon when circumstances permit, 6. Sitting and talking to someone, 7. Sitting quietly after a lunch without alcohol, and 8. In a car, while stopped for a few minutes in the traffic. Use the following scale to choose the most appropriate number for each situation: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 3 = high chance of dozing. Total ESS was calculated as the sum of all the individual scores observed for the above mentioned situations. The possible range for total ESS was 0-24. A lower total ESS indicates better sleep. | Day 29 | 
| Number of Snores Per Hour : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the number of snores per hour during the participant's domiciled sleep visits. Numbers of snores were recorded for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Snoring Percent of Sleep Time : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the snoring percent (%) present in sleep time during the participant's domiciled sleep visits. Snoring % was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Average Snore Sound Intensity : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the average snore sound intensity during the participant's domiciled sleep visits. Average snore sound intensity was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Peak Sore Sound Intensity : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the peak snore sound intensity during the participant's domiciled sleep visits. Peak snore sound intensity was recorded for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Percentage of Participants With Nasal Breathing Route : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the Nasal breathing route during the participant's domiciled sleep visits. Nasal breathing route was observed for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Percentage of Participants With Oro-nasal Breathing Route : Baseline, Active and Nasal Resistance Phase | The Investigator or designee recorded the oro-nasal breathing route during the participant's domiciled sleep visits. Oro-nasal breathing route was observed for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Total Sleep Time (TST) : Baseline, Active and Nasal Resistance Phase | TST was measured by overnight polysomnography (PSG) using a computerized system. TST was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Sleep Efficiency (SE) : Baseline, Active and Nasal Resistance Phase | Sleep efficiency [SE, a polysomnography (PSG)] was measured as the percentage of total time in bed spent in sleep. It was calculated as the sum of Stage N1, Stage N2, Stage N3, and REM sleep, divided by the total time in bed and multiplied by 100. SE gives an overall sense of how well the participant slept and was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Sleep Onset Latency (SOL) : Baseline, Active and Nasal Resistance Phase | Sleep onset latency (SOL, a PSG parameter) was measured as the duration from the time when lights were turned off (as the participants attempted to sleep) till the time participant fell asleep. Determination of sleep and awake state was based on Electroencephalography (EEG) and behavioral parameters change. SOL was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Arousal Index (AI) : Baseline, Active and Nasal Resistance Phase | Arousal index (AI) is the number of arousals and awakenings, reported as a total number per hour of sleep. AI was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Sleep Architecture (Non-Rapid Eye Movement- Stages N1, N2 and N3) : Baseline, Active and Nasal Resistance Phase | Non-Rapid eye movement (NREM) sleep stage consist of 3 progressively deeper stages of sleep: N1 (transition period from being awake to falling asleep), N2 (where breathing and heart rate began to slow) and N3 (slow wave sleep where body heals and repair itself). Sleep architecture (SA) was measured by the percentage of sleep time spent by the participants in each stage (time spent in each stage to total time spent in NREM, multiplied by 100). SA was measured for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Total Non-rapid Eye Movement (NREM) and Rapid Eye Movement (REM) Sleep : Baseline, Active and Nasal Resistance Phase | Total NREM (N1, 2, and 3) and REM sleep were calculated as the time spent by a participant in the NREM (measured during stable sleep) and REM sleep stages. Total NREM and REM sleep was measured by overnight PSG using a computerized system for all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Respiratory Effort Related Arousals (RERA) : Baseline, Active and Nasal Resistance Phase | Respiratory Effort Related Arousal (RERA) was flattening of an inspiratory portion of nasal pressure with increased respiratory effort leading to arousal. The total number of arousals per hour were calculated as RERA. RERA was measured all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Percentage of Lowest Arterial Oxygen Saturation (SAO2) During Rapid Eye Movement (REM) and Non-rapid Eye Movement (REM) Sleep Stage : Baseline, Active and Nasal Resistance Phase | Arterial oxygen saturation (SAO2) is the fraction of [oxygen]-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood. SAO2 in NREM and REM sleep was measured overnight by pulse oximetry with a finger probe using a computerized system. Lowest SAO2 values observed during the NREM and REM sleep were recorded for this endpoint. Oximetry measurements were performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Mean Arterial Oxygen Saturation (SAO2) During Sleep Time : Baseline, Active and Nasal Resistance Phase | SAO2 in sleep time was measured overnight by pulse oximetry with a finger probe using a computerized system. Mean of the observed SAO2 values during entire sleep time was reported for this endpoint. Oximetry measurements were performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Average Oxygen Desaturation During Sleep : Baseline, Active and Nasal Resistance Phase | Oxygen desaturation is the drop in blood's oxygen level per hours of sleep. Average drop in oxygen level during total sleep was measured overnight by pulse oximetry with a finger probe using a computerized system. Oximetry measurements were performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Percentage of Sleep Time With Arterial Oxygen Saturation (SAO2) Greater Than 90% : Baseline, Active and Nasal Resistance Phase | Percent sleep time with SAO2 greater than 90% was measured overnight by pulse oximetry with a finger probe. Oximetry measurements were performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Percentage of Sleep Time With Arterial Oxygen Saturation (SAO2) Less Than 90% : Baseline, Active and Nasal Resistance Phase | Percent sleep time with SAO2 less than 90% was measured overnight by pulse oximetry with a finger probe. Oximetry measurements were performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 
| Apnea/Hypopnea Index (AHI) : Baseline, Active and Nasal Resistance Phase | Apnea/Hypopnea Index (AHI) was measured as the number of events (apnea and hypopnea) per hour of sleep. AHI was measured using overnight by PSG using a computerized system. PSG was performed in all participants with strip on Day 1 (Visit 2) in baseline phase, Day 8 (Visit 3) and Day 29 (Visit 4) in active phase, and in participants with and without strip on Day 30 (Visit 5) and Day 31 (Visit 6) cumulatively, in nasal resistance phase. | Day 1, Day 8, Day 29, Day 30 and Day 31 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nasal dilator strip, Sleep disordered breathing