Stacking Exercises Aid the Decline in FVC and Sick Time

Duchenne Muscular Dystrophy Clinical Trial

— STEADFAST  

Official title:

Stacking Exercises Attenuate the Decline in Forced Vital Capacity and Sick Time (STEADFAST)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01999075
• Other study ID #: 12/26E
• Status: Completed
• Phase: Phase 4
• Start date: March 2013
• Est. completion date: November 22, 2018

Study information

• Verified date: December 2018
• Source: Children's Hospital of Eastern Ontario
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: November 22, 2018
• Est. primary completion date: November 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

Inclusion Criteria:

• Age 6-16 years - This age range was selected as there are accepted normative pulmonary function data and children 6 years of age and older are generally able to reliably perform pulmonary function tests. Children are followed in participating centres until they reach 18 years of age (allowing two years of follow-up).

• Clinical phenotypic features consistent with DMD and confirmed by either: (1) Muscle biopsy showing complete dystrophin deficiency; (2) Genetic test positive for deletion or duplication in the dystrophin gene resulting in an 'out-of-frame' mutation; or (3) Dystrophin gene sequencing showing a mutation associated with DMD.

• FVC = 30% predicted - This range of pulmonary function was selected to exclude those with severe restrictive respiratory impairment, who are less likely to be able to reliably perform pulmonary function testing over a two year period.

• A caregiver willing to provide the therapy

• Fluency in English or French

Exclusion Criteria:

• Unable to perform pulmonary function tests and/or LVR manoeuvre

• Presence of an endotracheal or tracheostomy tube

• Already using LVR and/or the Respironics in-exsufflator between and during respiratory infections

• Known susceptibility to pneumothorax or pneumomediastinum

• Uncontrolled asthma or other obstructive lung disease

• Symptomatic cardiomyopathy (ejection fraction less than 50% )

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Device:
• Lung Volume Recruitment (LVR)
LVR will be used twice per day

Other:
• 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

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	London Health Sciences	London	Ontario
Canada	Hôpital Ste. Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Holland Bloorview Kids Rehabilitation Hospital	Toronto	Ontario
Canada	SickKids Hospital	Toronto	Ontario
Canada	BC Children's Hospital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Eastern Ontario	Jesse's Journey-The Foundation for Gene and Cell Therapy

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximal and average pressure achieved with LVR (cmH2O)		2 years
Other	Respiratory symptoms	Respiratory symptoms, as assessed every 3 months by phone and personnel interview at clinic visits (Appendix 10_A self-report usage diary (Appendix 12)will be given to the participant to record daily activities to help with recall at the telephone follow ups	2 years
Other	Satisfaction with LVR	Satisfaction with LVR, as assessed every 3 months by phone	2 years
Primary	Relative decline in FVC (%-predicted) over 2 years, measured according to American Thoracic Society (ATS) standards, using the Stanojevic normative equations.	Relative decline 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 decline is an appropriate clinical laboratory measure and valid surrogate endpoint to use for this trial.	2 years
Secondary	Time to FVC decline of 10% of predicted.		2 years
Secondary	Total number and duration of outpatient oral antibiotic courses, hospital and ICU admissions for respiratory exacerbations over 2 years		2 years
Secondary	Health-related quality of life over 2 years	Measured biannually with PedsQL 4.0, Pediatric Quality of Life Inventory	2 years
Secondary	Change in unassisted peak cough flow (PCF), maximal insufflation capacity (MIC), maximum inspiratory and expiratory pressures (MIP, MEP), as well as MIC and PCF with LVR, over 2 years		2 years