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

Autor: N. N. J. Rommelse, A. R. Müller, Kit C.B. Roes, J. R. Zinkstok, E. de Rooij-Askes, Erik Boot, A. M. van Eeghen, P. M. van de Ven, C. Linders, Frits A. Wijburg
Přispěvatelé: APH - Methodology, Pediatric surgery, Paediatric Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Paediatric Genetics, APH - Personalized Medicine, APH - Aging & Later Life
Jazyk: angličtina
Rok vydání: 2021
Předmět:
N of 1 trial
medicine.medical_specialty
Multiple crossover
law.invention
Goal Attainment Scaling
All institutes and research themes of the Radboud University Medical Center
Randomized controlled trial
Double-Blind Method
law
Intellectual disability
mental disorders
medicine
Attention deficit hyperactivity disorder
Humans
ADHD
Pharmacology (medical)
Genetics (clinical)
Randomized Controlled Trials as Topic
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Methylphenidate
business.industry
Research
General Medicine
Strengths and Difficulties Questionnaire
medicine.disease
Smith–Magenis syndrome
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
Treatment Outcome
Attention Deficit Disorder with Hyperactivity
Physical therapy
Medicine
Central Nervous System Stimulants
Smith-Magenis Syndrome
business
N-of-1
Rare genetic neurodevelopmental disorder
medicine.drug
Zdroj: Orphanet Journal of Rare Diseases, 16(1):380. BioMed Central
Orphanet Journal of Rare Diseases, 16, 1
Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-9 (2021)
Orphanet Journal of Rare Diseases, 16
Orphanet Journal of Rare Diseases
Müller, A R, Zinkstok, J R, Rommelse, N N J, van de Ven, P M, Roes, K C B, Wijburg, F A, de Rooij-Askes, E, Linders, C, Boot, E & van Eeghen, A M 2021, ' 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, vol. 16, no. 1, 380 . https://doi.org/10.1186/s13023-021-02003-z
Orphanet journal of rare diseases, 16(1):380. BioMed Central
ISSN: 1750-1172
DOI: 10.1186/s13023-021-02003-z
Popis: Background Smith–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 analysis We 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. Conclusions This 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).
Databáze: OpenAIRE
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