Stacking Exercises Aid the Decline in FVC and Sick Time

NCT ID: NCT01999075

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2018-11-22

Brief 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.

Detailed 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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Conventional Treatment

Conventional Treatment

Group Type: PLACEBO_COMPARATOR

Conventional Treatment

Intervention Type: 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

Lung Volume Recruitment

Conventional treatment plus the use of Lung Volume Recruitment (LVR) twice per day

Group Type: ACTIVE_COMPARATOR

Lung Volume Recruitment (LVR)

Intervention Type: DEVICE

LVR will be used twice per day

Conventional Treatment

Intervention Type: 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

Interventions

Lung Volume Recruitment (LVR)

LVR will be used twice per day

Intervention Type: DEVICE

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

Intervention Type: OTHER

Eligibility Criteria

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% )

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jesse's Journey

OTHER

Sponsor Role: collaborator

Children's Hospital of Eastern Ontario

OTHER

Sponsor Role: lead

Responsible Party

Sherri Katz

Dr. Sherri Katz

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sherri Katz, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Eastern Ontario

Ian MacLusky, MD

Role: STUDY_DIRECTOR

Children's Hospital of Eastern Ontario

Nicholas Barrowman, PhD

Role: STUDY_DIRECTOR

Children's Hospital of Eastern Ontario

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

BC Children's Hospital

Vancouver, British Columbia, Canada

McMaster University

Hamilton, Ontario, Canada

London Health Sciences

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, Canada

SickKids Hospital

Toronto, Ontario, Canada

Hôpital Ste. Justine

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 35236763 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33887060 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

12/26E

Identifier Type: -

Identifier Source: org_study_id