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1 year update Guanabenz VWM clinical trial

The first trial participant was included on May 31st 2021. In the first year, 17 children have been included who are treated with Guanabenz (8 boys and 9 girls). The inclusion rate is faster than expected and we are ahead of schedule. Therefore we asked permission from the Dutch authorities for the possibility to include more children in the trial, up to 40.

The age of the children on entering the trial ranged between the 2 and 12 years. The disease duration when entering the trial ranged between the 1 and 8 years.

During the first visit to Amsterdam, the participants are titrated to the maximum tolerated dose of Guanabenz, which implies that all participants have temporary side effects. The minimum required dose of Guanabenz of 1 mg/kg/day was reached in all patients without major side effects. The final dose after the titration phase ranges between 1 and 2 mg/kg/day for the whole patient group. No children have been dosed above the 2 mg/kg/day. Initially, some children have to get used to swallowing the Guanabenz capsules, but after 1 or 2 weeks they all ingest the medication without problems, even the very young children.

All patients experienced the side-effects of sleepiness and drowsiness, as expected. Other important temporary side effects are: feeling unsteady/insecure (“wobbliness” as most children describe it themselves), dry mouth, constipation, nausea and vomiting. In some patients we also observed psychological effects like sad feelings, vivid dreams, nightmares and sometimes visual or tactile hallucinations. It sometimes takes time before the side-effects have resolved; this is different for each child. What we see is that after 3 months almost all children are back to normal, i.e. back in the condition before they entered the trial. To resolve side-effects more quickly it helps for some children to split the dose into two smaller gifts with an interval of several hours. In some cases (temporary) reduction of the dose of Guanabenz or extra medication is necessary (e.g. forlax to treat and prevent constipation, anti-emetics for vomiting, and risperdone to treat hallucinations).

Conclusion

Overall, the Guanabenz is tolerated by the children. There are no major side effects and no important safety issues. The monitor boards gave their permission to continue the trial in its present form. Longer follow-up is needed to determine the efficacy of Guanabenz. On 31st May 2022 we entered the second study year of the Guanabenz trial.

For more information about the Guanabenz clinical trial, visit our clinical trial page.