Trial Outcomes & Findings for Researching the Effects of Airway Clearance Therapies in Cystic Fibrosis (NCT NCT03078127)
NCT ID: NCT03078127
Last Updated: 2019-03-05
Results Overview
As described in the protocol, gamma scintigraphy was used to measure clearance of particles from the whole right lung region of interest over 274 minutes. The primary outcome for this study was the area under the particle clearance curve from time 0 to 274 minutes post-inhalation (normalized to time by dividing by 274) and expressed as a percent, representing total average rate of mucociliary clearance (MCC).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
10 participants
Primary outcome timeframe
274 minutes
Results posted on
2019-03-05
Participant Flow
Patients were screened and recruited from the adult CF clinic at UNC from January 2017 to December 2017.
Following screening, patients performed a baseline study visit prior to randomization into the study arms which determined which order to complete the other three interventions would be performed. Baseline (or "huff-cough") was completed prior to randomization to ensure comparator data if a patient was unable to complete the study.
Participant milestones
| Measure |
Sequence A
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), Whole body vibration, Vest, Oscillatory Positive Expiratory Pressure (OPEP).
(note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
Sequence B
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), Vest, OPEP, Whole body vibration (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
Sequence C
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), OPEP, Whole body vibration, Vest (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
|---|---|---|---|
|
First Intervention
STARTED
|
4
|
3
|
3
|
|
First Intervention
COMPLETED
|
4
|
3
|
3
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout (3-21 Days)
STARTED
|
4
|
3
|
3
|
|
Washout (3-21 Days)
COMPLETED
|
4
|
3
|
3
|
|
Washout (3-21 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
4
|
3
|
3
|
|
Second Intervention
COMPLETED
|
4
|
3
|
3
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
0
|
|
Third Intervention
STARTED
|
4
|
3
|
3
|
|
Third Intervention
COMPLETED
|
4
|
3
|
3
|
|
Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Researching the Effects of Airway Clearance Therapies in Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Sequence A
n=4 Participants
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), Whole body vibration, Vest, OPEP (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
Sequence B
n=3 Participants
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), Vest, OPEP, Whole body vibration (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
Sequence C
n=3 Participants
In this arm, the interventions were performed in the following order:
Baseline (prior to randomization), OPEP, Whole body vibration, Vest (note this is different than the sequence shown in the example latin square shown in the included protocol, as that was meant to serve as an example -- actual randomization and formulation of the employed latin square / sequence generator was performed following completion of the protocol)
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
42.25 years
n=5 Participants
|
37.67 years
n=7 Participants
|
41 years
n=5 Participants
|
40.5 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 274 minutesAs described in the protocol, gamma scintigraphy was used to measure clearance of particles from the whole right lung region of interest over 274 minutes. The primary outcome for this study was the area under the particle clearance curve from time 0 to 274 minutes post-inhalation (normalized to time by dividing by 274) and expressed as a percent, representing total average rate of mucociliary clearance (MCC).
Outcome measures
| Measure |
Huff-Cough Alone
n=10 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=10 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=10 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=10 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Mucociliary Clearance-274
|
20.3 percent clearance
Standard Error 2.6
|
16.8 percent clearance
Standard Error 3.1
|
18.5 percent clearance
Standard Error 2.8
|
19.1 percent clearance
Standard Error 2.3
|
SECONDARY outcome
Timeframe: 90 minutesPopulation: All subjects were included for analysis
As described in the protocol, gamma scintigraphy was used to measure clearance of particles from the whole right lung region of interest over 274 minutes. This outcome for this study was the area under the particle clearance curve from time 0 to 90 minutes post-inhalation (normalized to time by dividing by 90) and expressed as a percent, representing average rate of mucociliary clearance (MCC) over 90 minutes.
Outcome measures
| Measure |
Huff-Cough Alone
n=10 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=10 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=10 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=10 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Mucociliary Clearance-90
|
13.8 percent clearance
Standard Deviation 6.2
|
12.6 percent clearance
Standard Deviation 5.9
|
12.4 percent clearance
Standard Deviation 7.3
|
12.8 percent clearance
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: pre-ACT (0-16 mins) and during ACT (16-50 mins)Population: Only 4 subjects were included due to poor quality data obtained for slope measurement due to subject movement during the study (other MCC data used area under the curve data from key frames in which there was no subject movement, which proved to be more reliable). This data was not analyzed statistically.
Change in slope of particle clearance curve between pre intervention and ACT period.
Outcome measures
| Measure |
Huff-Cough Alone
n=4 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=4 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=4 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=4 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Change in Rate of MCC
|
0.011 %clearance / minute
Interval 0.001 to 0.023
|
.013 %clearance / minute
Interval 0.004 to 0.026
|
0.011 %clearance / minute
Interval -0.004 to 0.027
|
0.010 %clearance / minute
Interval 0.001 to 0.017
|
SECONDARY outcome
Timeframe: pre and immediately post intervention (50 mins post inhalation)Population: Only subjects who had measurable FENO above detection limits of the device (i.e. \<5 ppm) for both before and after ACT were included in analysis. Data from subjects during interventions who did not have a detectable FENO for both pre- and post- ACT were excluded for analysis.
FENO measurements were obtained pre- and post- intervention. The difference of post- vs pre- ACT FENO was reported.
Outcome measures
| Measure |
Huff-Cough Alone
n=8 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=8 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=6 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=6 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Change in Fraction of Exhaled Nitric Oxide (FENO)
|
-1.84 ppm of NO
Standard Deviation 3.36
|
-1.81 ppm of NO
Standard Deviation 2.65
|
-1.42 ppm of NO
Standard Deviation 5.41
|
-.75 ppm of NO
Standard Deviation 1.80
|
SECONDARY outcome
Timeframe: pre and immediately post intervention (50 mins post inhalation)Exhaled breath condensate was collected using a commercial device for this purpose. Concentrations of the purine adenosine monophosphate (AMP) and urea in this liquid were determined using mass spectrometry. This outcome was the difference in concentrations of AMP normalized to urea in this exhaled breath condensate between post-ACT and pre-ACT intervention.
Outcome measures
| Measure |
Huff-Cough Alone
n=10 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=10 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=10 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=10 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Purine Analysis (AMP) in Exhaled Breath Condensate
|
-0.206 unitless ratio (AMP/Urea conc.)
Standard Deviation 0.679
|
-.101 unitless ratio (AMP/Urea conc.)
Standard Deviation 0.124
|
-.036 unitless ratio (AMP/Urea conc.)
Standard Deviation 0.650
|
0.144 unitless ratio (AMP/Urea conc.)
Standard Deviation 0.406
|
SECONDARY outcome
Timeframe: pre and immediately post intervention (50 mins post inhalation)Difference of concentration of adenosine (a purine) in EBC between post-ACT and pre-ACT intervention.
Outcome measures
| Measure |
Huff-Cough Alone
n=10 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=10 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=10 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=10 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Purine Analysis (Adenosine) in Exhaled Breath Condensate (EBC)
|
-0.042 unitless ratio (adenosine/Urea conc.)
Standard Deviation 0.166
|
-0.027 unitless ratio (adenosine/Urea conc.)
Standard Deviation 0.065
|
-0.057 unitless ratio (adenosine/Urea conc.)
Standard Deviation 0.134
|
-.005 unitless ratio (adenosine/Urea conc.)
Standard Deviation 0.057
|
SECONDARY outcome
Timeframe: pre and immediately post intervention (50 mins post inhalation)Difference of concentration of hypoxanthine (a purine) in Exhaled Breath Condensate between post-ACT and pre-ACT intervention.
Outcome measures
| Measure |
Huff-Cough Alone
n=10 Participants
Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
Huff-Cough alone: Subjects will provide two "huffs" (forced expiratory maneuver with open glottis) followed by a cough every six minutes for a total of six Huff-Coughs.
|
Oscillatory Positive Expiatory Pressure Device (OPEP)
n=10 Participants
Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
Oscillatory Positive Expiatory Pressure Device: Subjects will use an Areobika® branded OPEP device (10 breaths through highest tolerated resistance) prior to undergoing a Huff-Cough. Subjects will use the device six times every six minutes.
|
Whole Body Vibration
n=10 Participants
Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
Whole-Body Vibration Platform: Subjects will be seated on a PowerPlate® whole-body vibration platform for 90 seconds prior to Huff-Cough. Six intervals on the platform will be completed six minutes apart.
|
High Frequency Chest Wall Oscillatory Vest (HFCWO)
n=10 Participants
Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
High Frequency Chest Wall Oscillatory Vest: Subjects will use TheVest® using a standardized "Minnesota Protocol" divided into six, four-minute segments, each followed by a Huff-Cough.
|
|---|---|---|---|---|
|
Purine Analysis (Hypoxanthine) in Exhaled Breath Condensate
|
-1.04 unitless ratio (adenosine/Urea conc.)
Standard Deviation 6.03
|
-1.93 unitless ratio (adenosine/Urea conc.)
Standard Deviation 4.16
|
1.64 unitless ratio (adenosine/Urea conc.)
Standard Deviation 7.81
|
0.760 unitless ratio (adenosine/Urea conc.)
Standard Deviation 1.88
|
Adverse Events
Huff-Cough Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Oscillatory Positive Expiatory Pressure Device (OPEP)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Whole Body Vibration
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Frequency Chest Wall Oscillatory Vest
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Scott Donaldson, MD
University of North Carolina at Chapel Hill
Phone: 984-974-9198
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place