Page 86 - Demo

Chapter 484Methods/DesignProtocol development and patient engagement The choice of TSC, MPS III, and FXS was based on the severe behavioral manifestations that are an important part of the phenotype and due to our experience with these patient groups. Representatives of the Dutch TSC and FXS patient advocacy organizations, caregivers of patients with TSC and FXS, and clinical experts of all patient groups played an important role in defining knowledge and care gaps, prioritizing the treatment study, selecting outcome measures and developing the current protocol. In the protocol, we have addressed concerns related to caregiver burden and patient burden of participation and issues for recruitment and retention. The Emma Children’s Hospital at the Amsterdam University Medical Center (UMC) is the national expertise center for MPS III. As a result, we have close contact with all Dutch families with MPS III. In addition, we have a longstanding experience in the treatment of behavioral and sleeping problems in these patients. Furthermore, we have a national clinic specialized in TAND at ‘s Heeren Loo and neuropsychiatric manifestations of FXS, collaborating closely with TSC and epilepsy expertise centers of the UMC Utrecht and expertise center of the University Medical Center of Rotterdam (ENCORE; Genetic NeuroCognitive Developmental Disorders Rotterdam Erasmus Medical Center (MC)). Study design and durationWe have used the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) extension for N-of-1 trials (SPENT) checklist that is aligned with the CONSORT (consolidated reporting items for trials) extension for N-of-1 trials (CENT) for developing this N-of-1 protocol.39The study will consist of a series of N-of-1 trials followed by an optional open-label extension phase. Each N-of-1 trial is block-randomized, placebo-controlled, and double-blinded with multiple crossovers in a single patient. The trial will start with a baseline period of two weeks without any intervention. A variable dose titration phase will follow with a taper period (two weeks) and washout period (one week) before starting the trial. Each Annelieke Muller sHL.indd 84 14-11-2023 09:07