Exercise Interventions in Huntington's Disease: An Individual Patient Data Meta-Analysis

Abstract

Background: Physical activity may be beneficial in Huntington's disease (HD); however, studies to date have been underpowered to detect change. We combined data from five randomized controlled feasibility trials using individual patient data meta-analyses. Methods/Design: All trial interventions comprised a combination of supervised and self-directed physical activity, with varied emphasis on aerobic, strength, endurance, flexibility, and task training. Duration ranged from 8 to 16 weeks. The primary outcome was the modified Unified Huntington's Disease Rating Motor Score. Secondary outcomes included the Symbol Digit Modality Test, Berg Balance Scale, 30-second Chair stand, Timed Up and Go, Gait Speed, Physical Performance Test, Six-Minute Walk, International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, EuroQol Health Utility Index, and Short-Form 36 Health Related Quality of Life Scale. The primary analysis utilized a two-stage approach. A one-stage approach was explored as a sensitivity analysis using a cross-classified (by study site) linear mixed-effects model. Results: One hundred twenty-one participants provided complete data. Risk of bias was moderate; however, primary outcomes were blind assessed. Primary pooled effect estimates adjusted for baseline modified motor score (95% confidence interval) were 0.2 (–2.1 to 2.6) favoring control. There was considerable heterogeneity between the studies. Conclusions: There was no evidence of an exercise effect on the modified motor score in these relatively short-duration interventions. Longer-duration trials incorporating supervised components meeting frequency, intensity, time, and type principles are required. Lack of common outcomes limited the analysis and highlight the importance of a core outcome set for evaluating exercise in HD.