Nasal Congestion
Conditions
Brief summary
The aim of the study is to evaluate the effect of the nasal strip (relative to the placebo strip) on the nasal passages using anatomical MRI scans and to demonstrate the effect of the strip on breathing correlated cortical activity, using interoceptive fMRI task and analysis techniques derived from physiological data collected during scanning.
Interventions
DEVICETest strip
Class I device for the application to the nose to facilitate better air flow through the nose
DEVICEPlacebo strip
Placebo strip
OTHERNasal spray
Nasal decongestant to be used on a single occasion (one spray per nostril), 20 minutes prior to commencing the third MRI scanning sessions.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants with a self-rating of at least 3 to 8 for nasal congestion on the numerical rating scale * Participants with a nasal congestion frequency score of 1, 2, 3 or 4.
Exclusion criteria
* Evidence of obstructive nasal polyps, nasal tract structural malformations, visible open sores, sunburn, irritation, eczema or chronic skin condition on the face or nose * Use of any medications like nasal decongestant, alpha adrenergic drugs, glucocorticoids and any current treatment which in the opinion of the investigator will affect nasal congestion * Known or suspected intolerance or hypersensitivity to the study materials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Measure: Blood Oxygen Level Dependent- Interoceptive Attention Task (Psychophysiological Interactive Analysis) | Upto 2.5 hours | Regional measures of functional brain activity were to be derived from a breathing-related interoceptive task. |
| Anatomical Measure: Volume (Single Volume Reading) | Upto 2.5 hours | Determination of single volume reading derived from examination of the nasal passages and sinuses, during the MRI. |
| Cerebral Blood Flow (CBF) | Upto 2.5 hours | CBF was derived from Arterial-Spin Labelling (ASL) scans. ASL data were analysed using custom Matlab code, which fits a CBF model to the raw perfusion data, in order to derive quantitative estimates of CBF in units of ml/100g/minute. The computed CBF maps were co-registered to the subject's whole-brain T1-weighted anatomical scan (from the first scan session) in order to spatially divide the data into anatomical Regions of Interest (ROIs). The anatomical ROIs were themselves defined by nonlinear warping of a standard cytoarchitectonic atlas into the space of the subject's T1 anatomical scan, using the FMRIB Software Library tool FNIRT. CBF data were extracted for a subset of these anatomical ROIs. |
| Anatomical Measures: Volume (Multiple Volume Reading) | Upto 2.5 hours | Determination of averaged volume reading during the MRI (Average of 8 sub-regions) |
| Anatomical Measures : Cross Sectional Area | Upto 2.5 hours | Determination of cross sectional area derived from examination of the nasal passages and sinuses using T1 weighted MRI scans. |
| Functional Brain Activity: Blood Oxygen Level Dependent- Interoceptive Attention Task | Upto 2.5 hours | Regional measures of functional brain activity to be derived from a breathing-related interoceptive task. This outcome measure was pre-specified to analyze effect on nasal strips on the functional brain activity without the use of nasal decongestant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application | Upto 30 minutes | Participants provided their response for VNR on a scale of 0 to 10 (0 = Breathe Freely and 10 = Totally Blocked) how easy it was to breathe through nose at a given time. |
| VNR: Change From Baseline to 20 Minutes After Decongestant Administration, and Post Application of the Marketed Nasal Strip After Decongestant Administration | Upto 2 hours | Participants provided their response for VNR on a scale of 0 to 10 (0 = Breathe Freely and 10 = Totally Blocked) how easy it was to breathe through nose at a given time. |
| Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State) | Upto 2.5 hours | Regional measures of breathing-related cortical activity were derived by determining Functional Connectivity and Event-related percentage signal change. Functional connectivity analyzes of fMRI data where spontaneous (i.e. while the participant is at rest) signal changes in one brain region are regressed against other regions, to identify regions sharing similar functional properties. Event-related functional magnetic resonance imaging (efMRI) detects changes in the BOLD hemodynamic response to neural activity associated with certain event. In this case, the events were pre-defined by collecting additional data during the scan; participant respiration was determined using a simple pressure-sensitive respiration belt. Events time-locked to peak inspiration and expiration were defined separately, and regressed against brain activity, showing brain regions that were more or less active during each event type. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited at a clinical site in London.
Pre-assignment details
A total of 35 participants were screened of which 28 were randomized in the study. Five of these did not meet study criteria, 1 had a protocol violation and 1 additional participant had other reason to leave the study, prior to be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants were randomized to receive either Marketed Nasal Strip or Placebo Nasal Strip (to be applied for up to two hours in either of the first two scans only). During the third scanning session, Marketed Nasal Strip was applied for approximately 20 minutes after administration of a Marketed Decongestant. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Other reason | 1 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 33.0 Years STANDARD_DEVIATION 10.98 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Anatomical Measures : Cross Sectional Area
Determination of cross sectional area derived from examination of the nasal passages and sinuses using T1 weighted MRI scans.
Time frame: Upto 2.5 hours
Population: Per-Protocol (PP) Population: Participants successfully completing all conditions of the experiment on single visit day except whose data didn't meet quality standards (problems with devices/software or participant (excessive head-motion during fMRI, inadequate performance of experimental tasks). Data of 7 participants didn't meet the standards.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Anatomical Measures : Cross Sectional Area | 133.22 mm^2 | Standard Deviation 28.946 |
| Placebo Nasal Strip | Anatomical Measures : Cross Sectional Area | 116.88 mm^2 | Standard Deviation 31.468 |
| Decongestant | Anatomical Measures : Cross Sectional Area | 156.48 mm^2 | Standard Deviation 29.103 |
| Test Nasal Strip Plus Decongestant | Anatomical Measures : Cross Sectional Area | 176.12 mm^2 | Standard Deviation 29.37 |
p-value: <0.000195% CI: [12.32, 18.25]ANOVA
Primary
Anatomical Measures: Volume (Multiple Volume Reading)
Determination of averaged volume reading during the MRI (Average of 8 sub-regions)
Time frame: Upto 2.5 hours
Population: Per-Protocol (PP) Population: Participants successfully completing all conditions of the experiment on single visit day except whose data didn't meet quality standards (problems with devices/software or participant (excessive head-motion during fMRI, inadequate performance of experimental tasks). Data of 7 participants didn't meet the standards.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Anatomical Measures: Volume (Multiple Volume Reading) | 1675.93 mm^3 | Standard Deviation 399.949 |
| Placebo Nasal Strip | Anatomical Measures: Volume (Multiple Volume Reading) | 1466.61 mm^3 | Standard Deviation 406.76 |
| Decongestant | Anatomical Measures: Volume (Multiple Volume Reading) | 1971.35 mm^3 | Standard Deviation 449.523 |
| Test Nasal Strip Plus Decongestant | Anatomical Measures: Volume (Multiple Volume Reading) | 2210.06 mm^3 | Standard Deviation 461.475 |
p-value: 0.163995% CI: [-78.62, 462.06]ANCOVA
Primary
Anatomical Measure: Volume (Single Volume Reading)
Determination of single volume reading derived from examination of the nasal passages and sinuses, during the MRI.
Time frame: Upto 2.5 hours
Population: Per-Protocol (PP) Population: Participants successfully completing all conditions of the experiment on single visit day except whose data didn't meet quality standards (problems with devices/software or participant (excessive head-motion during fMRI, inadequate performance of experimental tasks). Data of 7 participants didn't meet the standards.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Anatomical Measure: Volume (Single Volume Reading) | 13407.42 mm^3 | Standard Deviation 3199.592 |
| Placebo Nasal Strip | Anatomical Measure: Volume (Single Volume Reading) | 11732.85 mm^3 | Standard Deviation 3254.077 |
| Decongestant | Anatomical Measure: Volume (Single Volume Reading) | 15770.79 mm^3 | Standard Deviation 3596.181 |
| Test Nasal Strip Plus Decongestant | Anatomical Measure: Volume (Single Volume Reading) | 17680.49 mm^3 | Standard Deviation 3691.798 |
p-value: 0.000495% CI: [794.16, 2273.32]ANOVA
Primary
Cerebral Blood Flow (CBF)
CBF was derived from Arterial-Spin Labelling (ASL) scans. ASL data were analysed using custom Matlab code, which fits a CBF model to the raw perfusion data, in order to derive quantitative estimates of CBF in units of ml/100g/minute. The computed CBF maps were co-registered to the subject's whole-brain T1-weighted anatomical scan (from the first scan session) in order to spatially divide the data into anatomical Regions of Interest (ROIs). The anatomical ROIs were themselves defined by nonlinear warping of a standard cytoarchitectonic atlas into the space of the subject's T1 anatomical scan, using the FMRIB Software Library tool FNIRT. CBF data were extracted for a subset of these anatomical ROIs.
Time frame: Upto 2.5 hours
Population: Decongestant and Test Nasal Strip Plus Decongestant groups were not evaluated in this outcome measure as it was pre-specified to to analyze effect of nasal strips on the cerebral blood without the use of nasal decongestant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Cerebral Blood Flow (CBF) | 85.80 ml/100g/min | Standard Deviation 23.351 |
| Placebo Nasal Strip | Cerebral Blood Flow (CBF) | 86.25 ml/100g/min | Standard Deviation 20.079 |
p-value: 0.727895% CI: [-3.06, 2.14]ANOVA
Primary
Functional Brain Activity: Blood Oxygen Level Dependent- Interoceptive Attention Task
Regional measures of functional brain activity to be derived from a breathing-related interoceptive task. This outcome measure was pre-specified to analyze effect on nasal strips on the functional brain activity without the use of nasal decongestant.
Time frame: Upto 2.5 hours
Population: Decongestant and Test Nasal Strip Plus Decongestant groups were not included in this outcome measure as it was pre-specified to analyze effect on nasal strips on the brain activity without the use of nasal decongestant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Functional Brain Activity: Blood Oxygen Level Dependent- Interoceptive Attention Task | 7.39 % Signal | Standard Deviation 9.858 |
| Placebo Nasal Strip | Functional Brain Activity: Blood Oxygen Level Dependent- Interoceptive Attention Task | 7.92 % Signal | Standard Deviation 8.246 |
p-value: 0.736695% CI: [-6.43, 4.57]ANCOVA
Primary
Functional Measure: Blood Oxygen Level Dependent- Interoceptive Attention Task (Psychophysiological Interactive Analysis)
Regional measures of functional brain activity were to be derived from a breathing-related interoceptive task.
Time frame: Upto 2.5 hours
Population: Decongestant and Test Nasal Strip Plus Decongestant groups were not included in this outcome measure as it was pre-specified to evaluate the effect on nasal strips on the measure of brain activity without the use of nasal decongestant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Nasal Strip | Functional Measure: Blood Oxygen Level Dependent- Interoceptive Attention Task (Psychophysiological Interactive Analysis) | 0.13 % signal change | Standard Deviation 0.123 |
| Placebo Nasal Strip | Functional Measure: Blood Oxygen Level Dependent- Interoceptive Attention Task (Psychophysiological Interactive Analysis) | 0.12 % signal change | Standard Deviation 0.161 |
p-value: 0.462195% CI: [-0.03, 0.07]ANOVA
Secondary
Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State)
Regional measures of breathing-related cortical activity were derived by determining Functional Connectivity and Event-related percentage signal change. Functional connectivity analyzes of fMRI data where spontaneous (i.e. while the participant is at rest) signal changes in one brain region are regressed against other regions, to identify regions sharing similar functional properties. Event-related functional magnetic resonance imaging (efMRI) detects changes in the BOLD hemodynamic response to neural activity associated with certain event. In this case, the events were pre-defined by collecting additional data during the scan; participant respiration was determined using a simple pressure-sensitive respiration belt. Events time-locked to peak inspiration and expiration were defined separately, and regressed against brain activity, showing brain regions that were more or less active during each event type.
Time frame: Upto 2.5 hours
Population: Decongestant and Test Nasal Strip Plus Decongestant groups were not included in this outcome measure as it was prespecified to evaluate the effect on nasal strips on the breathing related brain activity without the use of nasal decongestant
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Nasal Strip | Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State) | Functional Connectivity (% signal change) | 0.42 % signal change | Standard Deviation 0.261 |
| Test Nasal Strip | Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State) | Event-related (% signal change) | 27.57 % signal change | Standard Deviation 40.038 |
| Placebo Nasal Strip | Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State) | Functional Connectivity (% signal change) | 0.33 % signal change | Standard Deviation 0.249 |
| Placebo Nasal Strip | Breathing-related Cortical Activity (Blood Oxygen Level Dependent- Resting State) | Event-related (% signal change) | 10.80 % signal change | Standard Deviation 43.793 |
Secondary
Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application
Participants provided their response for VNR on a scale of 0 to 10 (0 = Breathe Freely and 10 = Totally Blocked) how easy it was to breathe through nose at a given time.
Time frame: Upto 30 minutes
Population: Per-Protocol (PP) Population: Participants successfully completing all conditions of the experiment on single visit day except whose data didn't meet quality standards (problems with devices/software or participant (excessive head-motion during fMRI, inadequate performance of experimental tasks). Data of 2 participants didn't meet the standards.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Nasal Strip | Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application | Immediate Change from Baseline (Units on a scale) | -0.46 Units on a scale | Standard Deviation 1.067 |
| Test Nasal Strip | Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application | 30 minutes Change from Baseline (Units on a scale) | -1.00 Units on a scale | Standard Deviation 1.296 |
| Placebo Nasal Strip | Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application | Immediate Change from Baseline (Units on a scale) | -0.07 Units on a scale | Standard Deviation 0.9 |
| Placebo Nasal Strip | Verbal Numerical Response (VNR): Change From Baseline to Immediately After Strip Application and 30 Minutes Post Application | 30 minutes Change from Baseline (Units on a scale) | -0.42 Units on a scale | Standard Deviation 1.629 |
Secondary
VNR: Change From Baseline to 20 Minutes After Decongestant Administration, and Post Application of the Marketed Nasal Strip After Decongestant Administration
Participants provided their response for VNR on a scale of 0 to 10 (0 = Breathe Freely and 10 = Totally Blocked) how easy it was to breathe through nose at a given time.
Time frame: Upto 2 hours
Population: Per-Protocol (PP) Population: Participants successfully completing all conditions of the experiment on single visit day except whose data didn't meet quality standards (problems with devices/software or participant (excessive head-motion during fMRI, inadequate performance of experimental tasks). Data of 2 participants didn't meet the standards.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Nasal Strip | VNR: Change From Baseline to 20 Minutes After Decongestant Administration, and Post Application of the Marketed Nasal Strip After Decongestant Administration | Change from baseline post-decongestant use | -1.35 Units on a scale | Standard Deviation 1.522 |
| Test Nasal Strip | VNR: Change From Baseline to 20 Minutes After Decongestant Administration, and Post Application of the Marketed Nasal Strip After Decongestant Administration | Change from baseline (Nasal Strip + Decongestant) | -1.69 Units on a scale | Standard Deviation 1.436 |