Effect of a multicomponent nutritional supplement on functional outcomes for Duchenne muscular dystrophy: A randomized controlled trial.

BACKGROUND & AIMS: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. Whilst effective treatments such as gene therapy are developed, families often seek complementary therapies such as nutrition supplements to help their son maintain function; however, there is limited evidence supporting the use of nutritional supplements in DMD. This study aimed to compare the effect of a Standard nutritional supplement with an Enhanced nutritional supplement combining three nutriceuticals on functional outcomes in ambulatory boys with Duchenne muscular dystrophy (DMD). DESIGN: A 50-week double blinded, randomized, controlled crossover trial was conducted in four Australian neuromuscular centres. Primary outcome measures were 6-min walk distance (6MWD) and community ambulation (StepWatch™ Activity Monitoring). Secondary outcome measures included body composition and quality of life. Serum 25-hydroxyvitamin D was measured. RESULTS: Twenty-seven boys completed the intervention. Traditional crossover analysis demonstrated the Enhanced supplement compared to the Standard supplement was associated with a difference of +12 (95% CI: -16, 40) metres in 6MWD, +0.5 (95% CI: -53, 54) inactive minutes per day and -95 (95% CI: -887, 696) steps per day. A mixed effect model indicated a potentially clinically important effect of the Enhanced supplement on the 6MWD of +31 (95% CI: -19, 81) metres. Mean serum 25 hydroxyvitamin D levels at week 50 was 94 (95% CI: 84, 104) nmol/L. There was no observable effect of either supplement regime on body composition or quality of life. CONCLUSIONS: Whilst a positive effect of the Enhanced supplement on functional outcomes was observed, this finding was inconclusive due to the small sample size. The results do not support the use of combined nutritional supplements to improve body composition or quality of life in DMD. A dose of 2000 IU vitamin D was an adequate dose to raise serum 25-hydroxyvitamin D over 50 weeks. CLINICAL TRIAL REGISTRY: Registry #: ACTRN12610000462088, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610000462088.

Assessment of disease progression in dysferlinopathy: A 1-year cohort study.

OBJECTIVE: To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. METHODS: One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis. RESULTS: The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint. CONCLUSION: Certain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials. CLINICALTRIALSGOV IDENTIFIER: NCT01676077.

Teaching Manually Assisted Cough to Caregivers of Children With Neuromuscular Disease.

BACKGROUND: Cough augmentation techniques are taught by health-care providers to improve secretion clearance and to help prevent respiratory infections in children with neuromuscular disease. There is some evidence of the effectiveness of a manually assisted cough when applied by health-care providers. However, it is unknown whether parents and caregivers may also be effective in applying manually assisted cough. The aim of this study was to evaluate whether parents and caregivers are effective at applying a manually assisted cough to a child with neuromuscular disease after being taught by a health-care provider. METHODS: For this prospective cohort study, children and their parents or caregivers were recruited from neuromuscular clinics in the Sydney Children's Hospitals Network. Cough peak flow was the outcome measure for the strength of the child's cough. Children were eligible to participate if their unassisted cough peak flow at baseline was <270 L/min. Parents and caregivers were taught a manually assisted cough by a physiotherapist before being measured. The cough peak flow was measured in the following order: (1) during an unassisted cough as baseline, (2) during a manually assisted cough performed by a physiotherapist, (3) during a manually assisted cough performed by a parent or caregiver, and (4) during an unassisted cough after intervention. RESULTS: Twenty-eight children (24 boys, 4 girls; mean ± SD age, 12 ± 3 y) completed the study. No clinically or statistically significant changes were found in the cough peak flow after the application of a manually assisted cough by parents or caregivers (95% CI -11 to 11 L/min) or by physiotherapists (95% CI -6 to 14 L/min). CONCLUSIONS: Parents and caregivers and health-care providers were ineffective at increasing cough peak flow in children with neuromuscular weakness when applying a manually assisted cough. A single training session was insufficient for a parent or caregiver to be able to apply a manually assisted cough effectively on his or her child with neuromuscular weakness. Further research is warranted to guide recommendations on how best to equip parents and caregivers with the skills to help manage children with neuromuscular disease.