Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome

22q11.2 Deletion Syndrome Clinical Trial

Official title: Effects of Modulation of the Dopaminergic System Using Risperidone on Memory and Executive Processes in Individuals With 22q11.2 Deletion Syndrome

Status Terminated

Clinical Trial Summary

Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with a high risk of psychiatric disorders, including schizophrenia spectrum disorders. This population is characterized by a particular neurocognitive profile and atypical brain development. Risperidone is a second-generation antipsychotic, inhibitor of dopaminergic receptors. Used in the treatment of psychosis, risperidone is frequently prescribed in 22q11DS, for example to treat a psychotic episode. Research on an animal model of 22q11DS (LgDel+/- mice) shows that administering an antipsychotic for 12 days during a critical period of brain development (adolescence) prevents deleterious neuronal changes and improves behavioral performance in mice. The aim of this study is therefore to replicate the results found in mice and to identify a long-term neuroprotective effect.

This study is inspired on the one hand by the families who share with us the difficulties of individuals affected by 22q11DS on a daily basis, but also by the encouraging results of studies conducted on mice.

Clinical Trial Description

In a double-blind placebo design, this study investigates the effects of a 12 weeks treatment of risperidone (vs placebo) for participants with 22q11DS without psychotic symptoms.

The research hypothesis of this study is that a short-term (12 weeks) risperidone (Risperdal®) treatment during a critical phase of development (adolescence) will result in improved cognitive performance and brain changes observable using brain imaging techniques (Magnetic resonance Imaging, MRI and Electroencephalography, EEG). In addition, the beneficial effects will be observable in a follow-up evaluation, 6 months after the of treatment.

Risperdal® is a marketed product and is listed in the Swiss Compendium (2015). However, it is not used according to its indication for the treatment of psychotic disorders. The treatment will be administered orally in the form of capsules containing the ground tablet in order to preserve the double-blind procedure (meaning that neither the examiner nor the patient knows whether the capsule contains the active ingredient risperidone or a placebo). The dose will be individually adjusted according to the weight of each participant. The lowest dose recommended in the Swiss Compendium is 0.25 mg/day for children. Therefore this dos will be prescribe at the beginning of the treatment and then gradually increased to 0.25 mg gradually over 7 days. For individuals weighing less than 50 kg, the recommended dose is 0.5 mg/day, this dose will not be exceeded for these individuals. For individuals over 50 kg, the recommended dose is 1 mg/day. this dose will not exceeded for individuals over 50 kg. However, in order to adapt as closely as possible to the different weight categories, a dose of 0.75 mg will be given to the 51 to 70 kg weight category, and a maximum dose of 1 mg to individuals over 70 kg. Treatment will also be discontinued in progressive stages over a period of two weeks.

Each participant will complete a series of evaluations including cognitive tests and brain imaging (MRI and EEG) on 3 occasions: the 1st before the treatment period (baseline), the 2nd at the end of the treatment period (short-term effect) and the 3rd 6 months after the end of treatment (long-term effect). ;

Related Conditions & MeSH terms

• 22q11.2 Deletion Syndrome
• Craniosynostoses
• DiGeorge Syndrome
• Marfan Syndrome
• Syndrome

• NCT number: NCT04639960
• Study type: Interventional
• Source: University of Geneva, Switzerland
• Status: Terminated
• Phase: N/A
• Start date: September 29, 2017
• Completion date: May 1, 2021