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| Name | Class |
|---|---|
| Jesse's Journey | OTHER |
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Duchenne Muscular Dystrophy is complicated by weak breathing muscles and lung infections. "Lung volume recruitment" is a technique performed using a face mask or mouthpiece and a hand-held resuscitation bag to stack breaths, inflate the lungs and help clear the airways of secretions by increasing the forcefulness of a cough. We believe this will slow down the steady loss of lung function, prevent lung infection, and improve quality of life. Our aim is to compare the outcome of a group of individuals with DMD treated with standard care to another group that also receives lung volume recruitment. If effective, this study will change clinical practice by including twice-daily treatment as part of the standard of care for individuals with DMD, in order to improve their lung health and quality of life.
Background: Respiratory complications are the primary cause of morbidity and mortality associated with childhood Duchenne Muscular Dystrophy (DMD). Involvement of the respiratory muscles leads to progressive hypoventilation and/or recurrent atelectasis and pneumonia secondary to decreased cough efficacy. Lung volume recruitment (LVR) is a means of stacking breaths to achieve maximal lung inflation (MIC), prevent micro-atelectasis, and improve cough efficacy. Although it has been recommended by some experts as the "standard of care" for individuals with neuromuscular disease, the strategy has not been widely implemented in DMD given the lack of clinical trials to date to support its efficacy as well as the additional burden of care required in a population already requiring multiple interventions.
Primary Objective: To determine whether LVR, in addition to conventional treatment, is successful in reducing decline from baseline in forced vital capacity (FVC) over 2 years (percent predicted, measured according to American Thoracic Society standards), compared to conventional treatment alone in children with DMD.
Secondary Objectives: To determine differences between children treated with LVR in addition to conventional treatment, compared to those treated with conventional treatment alone, in: (1) the number of courses of antibiotics, hospitalizations and intensive care admissions for respiratory exacerbations, (2) health-related quality of life, and (3) peak cough flow and other pulmonary function tests.
Methods: We propose a 3-year multi-centre randomized controlled trial involving fifteen tertiary care pediatric hospitals across Canada. The study population consists of boys aged 6-16 years with DMD and FVC ≥ 30% of predicted. A sample size of 110 participants will be enrolled. This has been informed by chart review and survey of participating centres to be feasible, and will be re-assessed with an ongoing internal pilot study. Intervention: Participants will be allocated with a minimization procedure to receive conventional treatment (non-invasive ventilation, nutritional supplementation, physiotherapy and/or antibiotics, as decided by the treating physician) or conventional treatment plus twice daily LVR exercises performed with an inexpensive, portable self-inflating resuscitation bag containing a one-way valve and a mouthpiece. Data Analysis: The primary outcome (change in percent predicted FVC over 2 years) will be compared between the two study groups using an analysis of co-variance (ANCOVA) that takes into account baseline FVC and minimization factors.
Importance: Decline in pulmonary function among children with DMD negatively affects quality of life and predicts mortality. The relatively simple strategy of LVR has the potential to optimize pulmonary function and reduce respiratory exacerbations, thereby improving quality of life for individuals with DMD. This study is novel in that it is the first randomized controlled trial of LVR. A major strength is that the results will give support or refute recommendations regarding inclusion of LVR in the standard of care for individuals with DMD worldwide.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional Treatment | Placebo Comparator | Conventional Treatment |
|
| Lung Volume Recruitment | Active Comparator | Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lung Volume Recruitment (LVR) | Device | LVR will be used twice per day |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in FVC (%-Predicted) From Baseline to 2 Years. | 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. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| FVC Decline of 10% of Predicted | The time to reach an FVC decline of 10% of predicted will be used to calculate a hazard ratio. | 2 years |
| Number of Participants Prescribed Outpatient Oral Antibiotic Courses Between Baseline and 2 Years |
| Measure | Description | Time Frame |
|---|---|---|
| Maximal and Average Pressure Achieved With LVR (cmH2O) | 2 years | |
| Respiratory Symptoms | Mean rate of symptom months over the study period. Symptom months are months with any respiratory symptom. | 2 years |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sherri Katz, MD | Children's Hospital of Eastern Ontario | Principal Investigator |
| Ian MacLusky, MD | Children's Hospital of Eastern Ontario | Study Director |
| Nicholas Barrowman, PhD | Children's Hospital of Eastern Ontario | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada | ||
| Stollery Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35236763 | Derived | Katz SL, Mah JK, McMillan HJ, Campbell C, Bijelic V, Barrowman N, Momoli F, Blinder H, Aaron SD, McAdam LC, Nguyen TTD, Tarnopolsky M, Wensley DF, Zielinski D, Rose L, Sheers N, Berlowitz DJ, Wolfe L, McKim D. Routine lung volume recruitment in boys with Duchenne muscular dystrophy: a randomised clinical trial. Thorax. 2022 Aug;77(8):805-811. doi: 10.1136/thoraxjnl-2021-218196. Epub 2022 Mar 2. | |
| 33887060 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Of the 70 enrolled children, four did not have reliable or reproducible FVC measurements at baseline and were excluded.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in FVC (%-Predicted) From Baseline to 2 Years. | 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. | 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. | Posted | Mean | Standard Deviation | Mean difference in FVC %-predicted | 2 years |
|
2 years (baseline to last follow-up at 2 years).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mild chest discomfort | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Discomfort associated with use of LVR |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sherri Katz (Principal Investigator) | CHEO Research Institute | 613-737-7600 | 2956 | skatz@cheo.on.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 4, 2015 | Aug 31, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| Conventional Treatment |
| Other |
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 number of participants who received any antibiotic courses between baseline and two years
| 2 years |
| Health-related Quality of Life From Baseline to 2 Years | 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. | 2 years |
| Change in Difference Between Assisted and Unassisted Peak Cough Flow (PCF) From Baseline to 2 Years | Change in the difference between assisted and unassisted peak cough flow (in liters per minute) from baseline to 2 years. | 2 years |
| Change in Maximal Insufflation Capacity (MIC)-Vital Capacity (VC) From Baseline to 2 Years | Change in maximal insufflation capacity (MIC)-vital capacity (VC) in liters from Baseline to 2 Years | 2 years |
| Change in Maximum Inspiratory Pressures (MIP), From Baseline to 2 Years | Change in maximum inspiratory pressures (MIP, in centimeters of water), From Baseline to 2 Years | 2 years |
| Change in Maximal Expiratory Pressures (MEP), From Baseline to 2 Years | Change in maximal expiratory pressures (MEP, in liters), From Baseline to 2 Years | 2 years |
| Edmonton |
| Alberta |
| TGG 2J3 |
| Canada |
| BC Children's Hospital | Vancouver | British Columbia | V6H 3V4 | Canada |
| McMaster University | Hamilton | Ontario | L8S 4K1 | Canada |
| London Health Sciences | London | Ontario | N6A 4G5 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| Holland Bloorview Kids Rehabilitation Hospital | Toronto | Ontario | M4G 1R8 | Canada |
| SickKids Hospital | Toronto | Ontario | M5G 1X8 | Canada |
| Hôpital Ste. Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Derived |
| Morrow B, Argent A, Zampoli M, Human A, Corten L, Toussaint M. Cough augmentation techniques for people with chronic neuromuscular disorders. Cochrane Database Syst Rev. 2021 Apr 22;4(4):CD013170. doi: 10.1002/14651858.CD013170.pub2. |
| Enrolled in drug trial |
|
| Became ineligible |
|
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| FVC | Median | Inter-Quartile Range | %-predicted |
|
| Wheelchair assisted | Count of Participants | Participants |
|
| Scoliosis | Count of Participants | Participants |
|
| Non-invasive ventilation | Count of Participants | Participants |
|
| Steroid use | Count of Participants | Participants |
|
| OG001 | 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 |
|
|
|
| Secondary | FVC Decline of 10% of Predicted | The time to reach an FVC decline of 10% of predicted will be used to calculate a hazard ratio. | 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. | Posted | Mean | Standard Error | Months (restricted mean) | 2 years |
|
|
|
| Secondary | Number of Participants Prescribed Outpatient Oral Antibiotic Courses Between Baseline and 2 Years | Total number of participants who received any antibiotic courses between baseline and two years | 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. | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Health-related Quality of Life From Baseline to 2 Years | 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. | Participants who received either Conventional Treatment or Conventional Treatment plus LVR. | Posted | Median | Inter-Quartile Range | score on a scale | 2 years |
|
|
|
| Secondary | Change in Difference Between Assisted and Unassisted Peak Cough Flow (PCF) From Baseline to 2 Years | Change in the difference between assisted and unassisted peak cough flow (in liters per minute) from baseline to 2 years. | 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. | Posted | Mean | Standard Deviation | PCF="liters per minute" | 2 years |
|
|
|
|
| Secondary | Change in Maximal Insufflation Capacity (MIC)-Vital Capacity (VC) From Baseline to 2 Years | Change in maximal insufflation capacity (MIC)-vital capacity (VC) in liters from Baseline to 2 Years | 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. | Posted | Mean | Standard Deviation | MIC-VC="Liter" | 2 years |
|
|
|
|
| Secondary | Change in Maximum Inspiratory Pressures (MIP), From Baseline to 2 Years | Change in maximum inspiratory pressures (MIP, in centimeters of water), From Baseline to 2 Years | 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. | Posted | Mean | Standard Deviation | "cm H2O" | 2 years |
|
|
|
|
| Secondary | Change in Maximal Expiratory Pressures (MEP), From Baseline to 2 Years | Change in maximal expiratory pressures (MEP, in liters), From Baseline to 2 Years | 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. | Posted | Mean | Standard Deviation | "cm H2O" | 2 years |
|
|
|
|
| Other Pre-specified | Maximal and Average Pressure Achieved With LVR (cmH2O) | Data not collected during the study. | Posted | 2 years |
|
|
| Other Pre-specified | Respiratory Symptoms | Mean rate of symptom months over the study period. Symptom months are months with any respiratory symptom. | Respiratory symptoms were collected by telephone every 3 months over the study period. | Posted | Mean | Standard Deviation | Months | 2 years |
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 0 |
| 30 |
| EG001 | 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 | 0 | 36 | 0 | 36 | 3 | 36 |
|
| Syncopal episode | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Probably related to LVR |
|
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| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |