Methylphenidate for ADHD in Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Common behavioural manifestations in SMS include hyperactivity, attention deficits, impulsivity and emotion dysregulation. As a result, many patients are diagnosed with attention-deficit/hyperactivity disorder (ADHD), a condition often treated with methylphenidate. However, the effectiveness of methylphenidate for ADHD symptoms in SMS is unknown and may be different for SMS than observed in the general population, due to different aetiology and presentation of symptoms. The current N-of-1 study is a series of double-blind randomized and placebo-controlled multiple crossover trials within six participants who are diagnosed with SMS and ADHD. Each N-of-1 trial consists of a baseline period, a dose titration phase, three cycles of alternating two 7-days intervention periods each followed by a 7-days washout period, and a follow-up measurement. The goal of the current project is to investigate the efficacy of methylphenidate for ADHD symptoms in SMS. We aim to aggregate data from a series of N-of-1 trials to investigate the effectiveness of methylphenidate for ADHD in SMS.

We hypothesize that methylphenidate improves ADHD manifestations in children and adults with SMS.

The primary outcome measure (SDQ subscale hyperactivity/inattention) will be measured daily at the end of the day, except for the dose titration phase. The shortened version of the EDI as one of the secondary outcome measures will also be measured daily. Both questionnaires will be filled out digitally by patients and/or primary caregivers using the app m-Path, Castor Electronic Data Capture (EDC) or by using paper forms. At the end of each interventional period, patients and/or primary caregivers and supervisors of daily activities if present will be called to evaluate GAS goals, to go through the Personal Questionnaire, and to discuss possible side effects by using a standardized checklist of side effects of methylphenidate. Three months after terminating the third cycle of the N-of-1 trial, an optional contact moment will take place for a follow-up measurement in which the questionnaires will be filled out and the goals and items of GAS and PQ will be discussed again.

Participants will receive twice daily methylphenidate or placebo.