Page 95 - Demo

Cannabidiol for severe behavioral manifestations in TSC, MPS III, and FXS934In case participants have epilepsy, a seizure diary will be used to evaluate change in seizure frequency.Hepatic enzyme levels (ALT, AST, and bilirubin) will be checked to monitor adverse effects.Trial proceduresDuring the N-of-1 trial, the final CBD dosage as determined by the dose titration phase or placebo will be administered twice daily. During washout periods, no study medication will be taken. N-of-1 trial: multiple crossover phasePrior to the start of the trials, the participant and substitute decision maker(s) will be seen at the clinic to discuss the procedure and sign for informed consent (Figure 2). Personalized goals with regard to GAS will be identified together with the treating physician, psychologist, patients and primary caregivers. Seizures semiology will be discussed in detail and classified according to the classification of the International League Against Epilepsy (ILAE).78 Reporting of seizure frequency (by patients or caregivers) will be assessed. The shortened version VABS-III will be filled out by the clinicians to determine whether the SRS-2 could be filled out during the trial.59 Optionally, EEG recordings will be performed at baseline. A two-week baseline period will follow without any intervention. The ABC, CGI, syndrome-specific outcome measures, ADAMS, SCQ, SRS-2 (if applicable), SSP-NL, and OBVL, will be filled out and seizures will be reported. These questionnaires can be completed within one hour. For children, the OBVL will be filled out by parents or primary caregivers if they have known the child for at least six months. The CGI can be completed in less than a minute by an experienced rater. A dose titration phase is followed by a taper period and washout period. During the dose titration phase, contact moments will take place (by phone) twice weekly, and hepatic enzyme levels will be measured. The individual N-of-1 trial consists of two cycles each containing one active treatment (A), one placebo treatment (B), run-in periods, taper periods, and washout periods. Medication will be administered at home, institution setting or day care by caregivers. The ABC irritability subscale will Annelieke Muller sHL.indd 93 14-11-2023 09:07