Trial Outcomes & Findings for Inhaled Fluticasone Effects on Upper Airway Patency in Obstructive Lung Disease (NCT NCT01554488)

Results Overview

Pressure at which the pharyngeal upper airway closes during stable non-REM sleep, measured as described in the referenced citation.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

25 participants

Primary outcome timeframe

16-week randomized controlled phase

Results posted on

2020-02-05

Participant Flow

subjects enrolled 3/12/2013-11/6/2015

28 subjects were eligible at V2 and entered the 2-week low dose fluticasone run-in phase, necessary to assess fluticasone adherence. Thereafter, three subjects withdrew consent and were not randomized. Thus, 25 subjects were randomized.

Participant milestones

Participant milestones
Measure	High Dose Inhaled Fluticasone High dose inhaled fluticasone (1,760mcg/day)	Low Dose Inhaled Fluticasone Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Overall Study STARTED	13	12
Overall Study COMPLETED	12	9
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The subject population also included those with COPD for which the numbers are reported in the next section.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High Dose Inhaled Fluticasone n=13 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=12 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=13 Participants	0 Participants n=12 Participants	0 Participants n=25 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=13 Participants	12 Participants n=12 Participants	24 Participants n=25 Participants
Age, Categorical >=65 years	1 Participants n=13 Participants	0 Participants n=12 Participants	1 Participants n=25 Participants
Age, Continuous	48.9 years STANDARD_DEVIATION 18 • n=13 Participants	37.3 years STANDARD_DEVIATION 14 • n=12 Participants	42.2 years STANDARD_DEVIATION 16.8 • n=25 Participants
Sex: Female, Male Female	4 Participants n=13 Participants	7 Participants n=12 Participants	11 Participants n=25 Participants
Sex: Female, Male Male	9 Participants n=13 Participants	5 Participants n=12 Participants	14 Participants n=25 Participants
Asthma randomized	9 Participants n=13 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.	11 Participants n=12 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.	20 Participants n=25 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.
Asthma completed the study	8 Participants n=12 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.	8 Participants n=9 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.	16 Participants n=21 Participants • The subject population also included those with COPD for which the numbers are reported in the next section.
Chronic Obstructive Pulmonary Disease (COPD) randomized	4 Participants n=13 Participants • subject population included those with asthma, reported in the previous section	1 Participants n=12 Participants • subject population included those with asthma, reported in the previous section	5 Participants n=25 Participants • subject population included those with asthma, reported in the previous section
Chronic Obstructive Pulmonary Disease (COPD) completed the study	4 Participants n=12 Participants • subject population included those with asthma, reported in the previous section	1 Participants n=9 Participants • subject population included those with asthma, reported in the previous section	5 Participants n=21 Participants • subject population included those with asthma, reported in the previous section

PRIMARY outcome

Timeframe: 16-week randomized controlled phase

Pressure at which the pharyngeal upper airway closes during stable non-REM sleep, measured as described in the referenced citation.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=12 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Upper Airway Critical Closing Pressure (Pcrit) at Week 16	-3.03 cmH2O Standard Deviation 3.66	-1.68 cmH2O Standard Deviation 2.16

SECONDARY outcome

Timeframe: 16-week randomized phase

Wakefulness tongue function was measured using the Iowa Oral Performance Instrument (IOPI) at anterior and posterior tongue locations, as described in the referenced citation. In brief, this instrument has a small-sized, air-filled plastic balloon, called sensor or bulb, which was inserted between the tongue blade and the roof of the mouth. At each location, the tongue strength was determined as the maximum pressure generated against the IOPI bulb during a forced tongue contraction. Several standardized trials were conducted to ensure reproducibility.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=12 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Tongue Strength at Anterior Location at Week 16	61 KiloPascals Standard Deviation 14.4	63.7 KiloPascals Standard Deviation 18.5

SECONDARY outcome

Timeframe: 16-week randomized phase

Wakefulness tongue function was measured using the Iowa Oral Performance Instrument (IOPI) at anterior and posterior tongue locations, as described in the referenced citation. In brief, this instrument has a small-sized, air-filled plastic balloon, called sensor or bulb, which was inserted between the tongue blade and the roof of the mouth. At each location, the tongue strength was determined as the maximum pressure generated against the IOPI bulb during a forced tongue contraction. Several standardized trials were conducted to ensure reproducibility.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=12 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Tongue Strength at Posterior Location at Week 16	55.5 KiloPascals Standard Deviation 11.7	58.1 KiloPascals Standard Deviation 16.7

SECONDARY outcome

Timeframe: 16-week randomized treatment phase

Wakefulness tongue function was measured using the Iowa Oral Performance Instrument (IOPI) at anterior and posterior tongue locations, as described in the referenced citation. In brief, this instrument has a small-sized, air-filled plastic balloon, called sensor or bulb, which was inserted between the tongue blade and the roof of the mouth. At each location, the tongue strength was determined as the maximum pressure generated against the IOPI bulb during a forced tongue contraction. Then, tongue fatigability was measured through a submaximal task, as the time (in seconds) able to maintain \> 50% of the above measured strength, at each location. Several standardized trials were conducted for each measure and at each location, to ensure reproducibility.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=12 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Tongue Fatigability at Anterior Location at Week 16	74.4 seconds Standard Deviation 53.3	78 seconds Standard Deviation 25.5

SECONDARY outcome

Timeframe: 16-week randomized treatment phase

Wakefulness tongue function was measured using the Iowa Oral Performance Instrument (IOPI) at anterior and posterior tongue locations, as described in the referenced citation. In brief, this instrument has a small-sized, air-filled plastic balloon, called sensor or bulb, which was inserted between the tongue blade and the roof of the mouth. At each location, the tongue strength was determined as the maximum pressure generated against the IOPI bulb during a forced tongue contraction. Then, tongue fatigability was measured through a submaximal task, as the time (in seconds) able to maintain \> 50% of the above measured strength, at each location. Several standardized trials were conducted for each measure and at each location, to ensure reproducibility.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=12 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Tongue Fatigability of Posterior Location at Week 16	53 seconds Standard Deviation 18	65.9 seconds Standard Deviation 23.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 16-week randomized treatment phase

Population: 1 subject in High dose and 2 subjects in Low dose inhaled fluticasone groups had contraindications, eg, metal in their bodies (2) or claustrophobia (1) and could not undergo MRI testing, per the set exclusion criteria.

Tongue volume was assessed on Magnetic Resonance (MR) imaging of the area extending from the level of the roof of the hard palate to the vocal cords, with the subject awake and lying on their back. We used a specialized technique called Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation Fast Spin-Echo (IDEAL-FSE), developed at University of Wisconsin by our collaborator and used for assessing the tongue (2). In brief, at first, the method provides well co-registered, separate water and fat images, which are free from the artifact that corrupts the usual MR images. Subsequently, these separate images are recombined in new high resolution images which provide: 1) comprehensive anatomical reference to delineate the tongue and measure its volume, and; 2) unambiguous separation of adipose tissue, to allow determination of fat volume and fraction in the tongue.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=11 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=7 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Tongue Volume at Week 16	73.2 mm^3 Standard Deviation 15.5	75.9 mm^3 Standard Deviation 15

OTHER_PRE_SPECIFIED outcome

Timeframe: 16-week randomized controlled phase

Population: 1 subject in High dose and 2 subjects in Low dose inhaled fluticasone groups had contraindications, eg, metal in their bodies (2) or claustrophobia (1) and could not undergo MRI testing, per the set exclusion criteria.

Tongue fat content was assessed on Magnetic Resonance (MR) imaging of the area extending from the level of the roof of the hard palate to the vocal cords, with the subject awake and lying on their back. We used a specialized technique called Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation Fast Spin-Echo (IDEAL-FSE), developed at University of Wisconsin by our collaborator and used for assessing the tongue (2). In brief, at first, the method provides well co-registered, separate water and fat images, which are free from the artifact that corrupts the usual MR images. Subsequently, these separate images are recombined in new high resolution images which provide: 1) comprehensive anatomical reference to delineate the tongue and measure its volume, and; 2) unambiguous separation of adipose tissue, to allow determination of fat volume and fraction in the tongue.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=11 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=7 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Percentage Fat Content (Fat Fraction) of the Tongue at Week 16	27.8 percentage of total tongue volume Standard Deviation 9.98	24.6 percentage of total tongue volume Standard Deviation 7.88

OTHER_PRE_SPECIFIED outcome

Timeframe: 16-week randomized controlled phase

Population: 1 subject in High dose and 2 subjects in Low dose inhaled fluticasone groups had contraindications, eg, metal in their bodies (2) or claustrophobia (1) and could not undergo MRI testing, per the set exclusion criteria.

The volume of pharyngeal upper airway surrounding structures was assessed on Magnetic Resonance (MR) imaging, as we published (1). We scanned the area extending from the level of the roof of the hard palate to the vocal cords, with the subject awake and lying on their back, We used a specialized technique called Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation Fast Spin-Echo (IDEAL-FSE). In brief, at first, the method provides well co-registered, separate water and fat images, which are free from the artifact that corrupts the usual MR images. Subsequently, these separate images are recombined in new high resolution images which provide: 1) comprehensive anatomical reference to delineate the tongue and measure its volume, and; 2) unambiguous separation of adipose tissue, to allow determination of fat volume and fraction in the upper airway structures.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=11 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=7 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Volume of Pharyngeal Upper Airway Surrounding Structures at Week 16	205 mm^3 Standard Deviation 67.9	194 mm^3 Standard Deviation 73.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 16-week randomized controlled phase

Population: 1 subject in High dose and 2 subjects in Low dose inhaled fluticasone groups had contraindications, eg, metal in their bodies (2) or claustrophobia (1) and could not undergo MRI testing, per the set exclusion criteria.

Pharyngeal upper airway fat content was assessed on Magnetic Resonance (MR) imaging, as we published (1). We scanned the area extending from the level of the roof of the hard palate to the vocal cords, with the subject awake and lying on their back, We used a specialized technique called Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation Fast Spin-Echo (IDEAL-FSE). In brief, at first, the method provides well co-registered, separate water and fat images, which are free from the artifact that corrupts the usual MR images. Subsequently, these separate images are recombined in new high resolution images which provide: 1) comprehensive anatomical reference to delineate the tongue and measure its volume, and; 2) unambiguous separation of adipose tissue, to allow determination of fat volume and fraction in the upper airway structures.

Outcome measures

Outcome measures
Measure	High Dose Inhaled Fluticasone n=11 Participants High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=7 Participants Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Percentage Fat Content (Fat Fraction) of Pharyngeal Upper Airway Surrounding Structures at Week 16	41.5 percentage of total airway volume Standard Deviation 24.6	31.5 percentage of total airway volume Standard Deviation 17.4

Adverse Events

High Dose Inhaled Fluticasone

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Low Dose Inhaled Fluticasone

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	High Dose Inhaled Fluticasone n=12 participants at risk High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 participants at risk Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Hepatobiliary disorders needed gallbladder surgery for stones	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Respiratory, thoracic and mediastinal disorders asthma exacerbation	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.

Other adverse events

Other adverse events
Measure	High Dose Inhaled Fluticasone n=12 participants at risk High dose inhaled fluticasone (1760mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid	Low Dose Inhaled Fluticasone n=9 participants at risk Low dose inhaled fluticasone (88mcg/day) Inhaled Fluticasone Propionate: Inhaled corticosteroid
Gastrointestinal disorders tongue lesion from broken tooth	0.00% 0/12 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Gastrointestinal disorders broken tooth	0.00% 0/12 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Respiratory, thoracic and mediastinal disorders bronchitis	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Respiratory, thoracic and mediastinal disorders asthma exacerbation	0.00% 0/12 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Respiratory, thoracic and mediastinal disorders hoarseness	25.0% 3/12 • Number of events 3 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	0.00% 0/9 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Respiratory, thoracic and mediastinal disorders URI	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Reproductive system and breast disorders yeast infection	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	0.00% 0/9 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Skin and subcutaneous tissue disorders rash	0.00% 0/12 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	11.1% 1/9 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.
Vascular disorders hypertension	8.3% 1/12 • Number of events 1 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.	0.00% 0/9 • from study initiation up to 16 weeks of randomized treatment. In addition, monitoring continued for an additional two months step-down inhaled fluticasone treatment under medical supervision by the study team.

Additional Information

Mihaela Teodorescu, MD-Principle Investigator

William S. Middleton Memorial VA Hospital

Phone: (608)2561901

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place