Trial Outcomes & Findings for Stacking Exercises Aid the Decline in FVC and Sick Time (NCT NCT01999075)

NCT ID: NCT01999075

Last Updated: 2025-01-09

Results Overview

Change in FVC (%-predicted) was chosen as the primary outcome as it is a strong predictor of subsequent respiratory failure and mortality. Although survival is not a realistic endpoint for this trial, given expected mortality is less than 5% for the pediatric age group, FVC change is an appropriate clinical laboratory measure and valid surrogate endpoint to use for this trial.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 70 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2025-01-09

Participant Flow

Participant milestones

Measure	Conventional Treatment Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Overall Study STARTED	33	37
Overall Study COMPLETED	28	25
Overall Study NOT COMPLETED	5	12

Reasons for withdrawal

Measure	Conventional Treatment Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Overall Study Lost to Follow-up	0	2
Overall Study Withdrawal by Subject	2	7
Overall Study Enrolled in drug trial	3	1
Overall Study Became ineligible	0	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Conventional Treatment n=30 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=36 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Total n=66 Participants Total of all reporting groups
Age, Continuous	11.5 years n=30 Participants	11.5 years n=36 Participants	11.5 years n=66 Participants
Sex: Female, Male Female	0 Participants n=30 Participants	0 Participants n=36 Participants	0 Participants n=66 Participants
Sex: Female, Male Male	30 Participants n=30 Participants	36 Participants n=36 Participants	66 Participants n=66 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
FVC	85.6 %-predicted n=30 Participants	84.0 %-predicted n=36 Participants	84.8 %-predicted n=66 Participants
Wheelchair assisted	10 Participants n=30 Participants	11 Participants n=36 Participants	21 Participants n=66 Participants
Scoliosis	3 Participants n=30 Participants	6 Participants n=36 Participants	9 Participants n=66 Participants
Non-invasive ventilation	2 Participants n=30 Participants	2 Participants n=36 Participants	4 Participants n=66 Participants
Steroid use	27 Participants n=30 Participants	32 Participants n=36 Participants	59 Participants n=66 Participants

PRIMARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized to a treatment arm, four children (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible pulmonary function test at baseline. All remaining children were included in the analyses except where no measurement was available.

Change in FVC (%-predicted) was chosen as the primary outcome as it is a strong predictor of subsequent respiratory failure and mortality. Although survival is not a realistic endpoint for this trial, given expected mortality is less than 5% for the pediatric age group, FVC change is an appropriate clinical laboratory measure and valid surrogate endpoint to use for this trial.

Outcome measures

Measure	Conventional Treatment n=25 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=28 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Change in FVC (%-Predicted) From Baseline to 2 Years.	-9.2 Mean difference in FVC %-predicted Standard Deviation 17.3	-6.4 Mean difference in FVC %-predicted Standard Deviation 15.7

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized to a treatment arm, four children (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible pulmonary function test at baseline. All remaining children were included in the analyses.

The time to reach an FVC decline of 10% of predicted will be used to calculate a hazard ratio.

Outcome measures

Measure	Conventional Treatment n=30 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=36 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
FVC Decline of 10% of Predicted	19.14 Months (restricted mean) Standard Error 1.59	21.70 Months (restricted mean) Standard Error 1.22

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized to a treatment arm, four children (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible pulmonary function test at baseline. All remaining children were included in the analyses except where no measurement was available.

Total number of participants who received any antibiotic courses between baseline and two years

Outcome measures

Measure	Conventional Treatment n=30 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=36 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Number of Participants Prescribed Outpatient Oral Antibiotic Courses Between Baseline and 2 Years	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Participants who received either Conventional Treatment or Conventional Treatment plus LVR.

Measured biannually using the Pediatric Quality of Life Inventory (PedsQL 4.0). The PedsQL includes four subscales: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Each subscale is scored from 0 to 100, with higher scores indicating better health-related quality of life. A total score is computed by averaging all subscale scores.

Outcome measures

Measure	Conventional Treatment n=23 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=25 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Health-related Quality of Life From Baseline to 2 Years	2.0 score on a scale Interval -7.8 to 6.8	3.8 score on a scale Interval -4.8 to 11.1

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized to a treatment arm, four children (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible pulmonary function test at baseline. All remaining children were included in the analyses except where no measurement was available.

Change in the difference between assisted and unassisted peak cough flow (in liters per minute) from baseline to 2 years.

Outcome measures

Measure	Conventional Treatment n=2 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=3 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Change in Difference Between Assisted and Unassisted Peak Cough Flow (PCF) From Baseline to 2 Years	-2.6 PCF="liters per minute" Standard Deviation 32.0	44.9 PCF="liters per minute" Standard Deviation 65.6

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized to a treatment arm, four children (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible pulmonary function test at baseline. All remaining children were included in the analyses except where no measurement was available.

Change in maximal insufflation capacity (MIC)-vital capacity (VC) in liters from Baseline to 2 Years

Outcome measures

Measure	Conventional Treatment n=7 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=9 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Change in Maximal Insufflation Capacity (MIC)-Vital Capacity (VC) From Baseline to 2 Years	0.1 MIC-VC="Liter" Standard Deviation 0.2	0.0 MIC-VC="Liter" Standard Deviation 0.2

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized, 4 (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible baseline pulmonary function tests. Results are for the observed population, as missing data imputation was not feasible. Of the remaining children, missing data was as follows: MIP and MEP (3 in conventional arm, 5 in LVR arm). A total of 16 children in the conventional group and 17 in the LVR group had useable data for MIP.

Change in maximum inspiratory pressures (MIP, in centimeters of water), From Baseline to 2 Years

Outcome measures

Measure	Conventional Treatment n=15 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=17 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Change in Maximum Inspiratory Pressures (MIP), From Baseline to 2 Years	-0.5 "cm H2O" Standard Deviation 15.7	-4.6 "cm H2O" Standard Deviation 25.1

SECONDARY outcome

Timeframe: 2 years

Population: Of the 70 children randomized, 4 (n=3 in conventional treatment group; n=1 in LVR group) were excluded from the analyses as they did not have a reliable or reproducible baseline pulmonary function tests. Results are for the observed population, as missing data imputation was not feasible. Of the remaining children, missing data was as follows: MIP and MEP (3 in conventional arm, 5 in LVR arm). A total of 16 children in the conventional group and 17 in the LVR group had useable data for MEP.

Change in maximal expiratory pressures (MEP, in liters), From Baseline to 2 Years

Outcome measures

Measure	Conventional Treatment n=16 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=17 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Change in Maximal Expiratory Pressures (MEP), From Baseline to 2 Years	5.5 "cm H2O" Standard Deviation 17.1	12.9 "cm H2O" Standard Deviation 19.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

Population: Data not collected during the study.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

Population: Respiratory symptoms were collected by telephone every 3 months over the study period.

Mean rate of symptom months over the study period. Symptom months are months with any respiratory symptom.

Outcome measures

Measure	Conventional Treatment n=28 Participants Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=32 Participants Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Respiratory Symptoms	0.08 Months Standard Deviation 0.14	0.12 Months Standard Deviation 0.29

Adverse Events

Conventional Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lung Volume Recruitment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Conventional Treatment n=30 participants at risk Conventional Treatment Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids	Lung Volume Recruitment n=36 participants at risk Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day Lung Volume Recruitment (LVR): LVR will be used twice per day Conventional Treatment: This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Respiratory, thoracic and mediastinal disorders Mild chest discomfort	0.00% 0/30 • 2 years (baseline to last follow-up at 2 years).	5.6% 2/36 • Number of events 2 • 2 years (baseline to last follow-up at 2 years).
Respiratory, thoracic and mediastinal disorders Syncopal episode	0.00% 0/30 • 2 years (baseline to last follow-up at 2 years).	2.8% 1/36 • Number of events 1 • 2 years (baseline to last follow-up at 2 years).

Additional Information

Dr. Sherri Katz (Principal Investigator)

CHEO Research Institute

Phone: 613-737-7600

Email: skatz@cheo.on.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place