Page 89 - Demo

Cannabidiol for severe behavioral manifestations in TSC, MPS III, and FXS874y Use of any interfering medication within 30 days prior to enrolment or planning to take interfering medication during the trial.y Any planned major surgery within the duration of the trial.y Expected inability to undergo blood sampling due to anxiety or resistance.y Unwillingness or inability to swallow the study drug (or placebo).In addition to the exclusion criteria, use of valproate should be stable three months prior to enrolment. Sample sizeThe sample size calculation was based on a summary measures analysis of the treatment effect.46 The difference between the mean irritability ratings of the Aberrant Behavior Checklist (ABC) in CBD periods and placebo periods was used as a summary measure for the treatment effect in an individual participant. Heussler et al. (2019) reported a standard deviation (SD) of 12 points for single ratings on the subscale.9 This estimate for the SD includes both within- and between-subject variance. The intraclass correlation coefficient (ICC) was assumed to be 0.75. In addition to the estimate for the within-subject variation of the outcome measure, an a priori estimate was needed for the between-subject variation of the treatment effect. Assuming an SD of 3 points for the SD of the random treatment effect, 95% of the subject-specific treatment effects roughly falls within a range of 12 points. Based on the estimate assuming two cycles with six ABC ratings within each period, a total of 6 participants will yield 80% power to detect a mean difference of 6 points between intervention and placebo periods when assuming a two-sided significance level of 5%. As effects for pediatric and adult population may differ, separate power analyses were performed for the pediatric and adult cohorts. Per cohort, this amounts to 6 pediatric patients and/or 6 adult patients, with a total inclusion of 12 patients with TSC, 12 with FXS and 6 pediatric patients with MPS III. MPS III is a type of childhood dementia and most patients never reach adulthood.26 Adult patients experience progressive dementia. This stage of the disease is not associated with severe behavioral manifestations, and therefore we will not include adult patients with MPS III.Annelieke Muller sHL.indd 87 14-11-2023 09:07