Page 65 - Demo

Methylphenidate for ADHD in Smith-Magenis syndrome633between intervention and placebo periods when assuming a two-sided significance level of 5%.RecruitmentStudy subjects will be recruited through the two national Dutch SMS multidisciplinary outpatient clinics of ‘s Heeren Loo, and the Dutch SMS patient advocacy organization.Trial procedure and study settingPrior to the start of the trials, the participant and substitute decision maker(s) will have a clinical visit to discuss the procedure in detail and sign the informed consent. Personalized goals with regard to GAS and the PQ and target symptoms will be identified together by the parents and/or primary caregivers, the treating physician, psychologist and/or behavioural therapist, and investigator. During the clinical visit, it will be emphasized that assessors should rate the global effect over the day and should be aware of the possible rebound effect of MPH. The study will be carried out at participants’ home setting and schools or daytime centres if applicable.The trial will start with a baseline period of seven days without any intervention. A dose titration phase of six days is followed by a washout period of eight days. The individual N-of-1 trial will consist of three cycles each containing four seven-day periods: one active treatment (A), one placebo treatment (B), and two ‘washout’ periods following A and B. The order in which patients receive active and placebo treatment is randomized within each cycle. The medication will be administered at home and/or at school or daytime activities by parents or primary caregivers. During the baseline period and three cycles, the SDQ and EDI will be filled out daily at the end of the day using app-based questionnaires by primary caregivers (Figure 2). Filling out the questionnaires will take about 1 min a day. At the end of each seven-day period, the investigator will interview patients and/or primary caregivers by phone to evaluate goals,33 to assess possible side effects, to note the general moments that the interventional effects seem to wear off, and to note the perceived treatment received (MPH or placebo). The time expected to complete this interview is 15 min. Each period will include a weekend such that parents can provide assessments of complete Annelieke Muller sHL.indd 63 14-11-2023 09:07