Methylphenidate for attention-deficit/hyperactivity disorder in patients with Smith–Magenis syndrome: protocol for a series of N-of-1 trials

Orphanet Journal of Rare Diseases

C. Linders¹  E. de Rooij-Askes¹  A. M. van Eeghen²  A. R. Müller²  E. Boot³  P. M. van de Ven⁴  K. C. B. Roes⁵  F. A. Wijburg⁶  J. R. Zinkstok⁷  N. N. J. Rommelse⁸ 

[1] Advisium, ’s Heeren Loo, Amersfoort, the Netherlands;Advisium, ’s Heeren Loo, Amersfoort, the Netherlands;Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands;Advisium, ’s Heeren Loo, Amersfoort, the Netherlands;Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands;The Dalglish Family 22Q Clinic, University Health Network, Toronto, ON, Canada;Department of Epidemiology and Data Science, Amsterdam University Medical Center, Amsterdam, The Netherlands;Department of Health Evidence, Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands;Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands;Department of Psychiatry and Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands;Karakter, Child and Adolescent Psychiatry, Nijmegen, The Netherlands;Department of Psychiatrics, Radboud University Medical Center, Nijmegen, The Netherlands;

关键词: N-of-1;    Smith–Magenis syndrome;    Methylphenidate;    Rare genetic neurodevelopmental disorder;    Multiple crossover;    ADHD;   

DOI  :  10.1186/s13023-021-02003-z

来源: Springer

【 摘 要 】

BackgroundSmith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations.Methods and analysisWe will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level.ConclusionsThis study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care.Trial registration This study is registered in the Netherlands Trial Register (NTR9125).

【 授权许可】

CC BY