Clinical trial NCT04639960: Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
Official title: Effects of Modulation of the Dopaminergic System Using Risperidone on Memory and Executive Processes in Individuals With 22q11.2 Deletion Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: 22q11.2 Deletion Syndrome
Lead sponsor: University of Geneva, Switzerland
Sponsor class: OTHER
First posted: 2020-11-23
Enrollment: 16
Sex: ALL
Minimum age (years): 11
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind placebo design
Primary purpose: OTHER

Brief 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.

Detailed 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).

Eligibility criteria: Inclusion Criteria:

* Male or female with confirmed 22q11DS diagnosis.
* Minimum age of 8 years or maximum age of 25 years and 11 months.
* Sufficient verbal expression and comprehension skills to understand and follow instructions based on initial interview.

Exclusion Criteria:

* Participants younger than 8 years and older that 25 years and 11 months.
* Previous adverse experience with risperidone
* Psychotic symptoms requiring sustained antipsychotic treatment
* Corrected QT (QTc) distance at baseline electrocardiogram above 460 milliseconds or elongation at control electrocardiogram (Day 6 of treatment) superior to 30 milliseconds with functional complaint.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Conners' Continuous performance test, third edition (CPT-3)
timeFrame: CPT-3 pre-treatment
measure: Conners' Continuous performance test, third edition (CPT-3)
timeFrame: CPT-3 One week after treatment
measure: Conners' Continuous performance test, third edition (CPT-3)
timeFrame: CPT-3 six month after treatment
measure: Stroop Task
timeFrame: Stroop inhibition ratio pre-treatment
measure: Stroop Task
timeFrame: Stroop inhibition ratio one week after treatment
measure: Stroop Task
timeFrame: Stroop inhibition ratio six month after treatment
measure: Letter-number sequencing
timeFrame: Letter-number Sequencing pre-treatment
measure: Letter-number sequencing
timeFrame: Letter-number Sequencing one week after treatment
measure: Letter-number sequencing
timeFrame: Letter-number Sequencing six month after treatment
measure: Color Trails test (CTT)
timeFrame: CTT flexibility ratio pre-treatment
measure: Color Trails test (CTT)
timeFrame: CTT flexibility ratio one week after treatment
measure: Color Trails test (CTT)
timeFrame: CTT flexibility ratio six month after treatment
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: CANTAB pre-treatment
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: CANTAB one week after treatment
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: CANTAB six month after treatment
measure: 15 signs & 15 words
timeFrame: 15 signs & 15 words pre-treatment
measure: 15 signs & 15 words
timeFrame: 15 signs & 15 words on week after treatment
measure: 15 signs & 15 words
timeFrame: 15 signs & 15 words six month after treatment
measure: Magnetic Resonance Imaging (MRI) T1-weighted
timeFrame: MRI T1-weighted pre-treatment
measure: Magnetic Resonance Imaging (MRI) T1-weighted
timeFrame: MRI T1-weighted one week after treatment
measure: Magnetic Resonance Imaging (MRI) T1-weighted
timeFrame: MRI T1-weighted six month after treatment
measure: MRI Spectroscopy
timeFrame: MRI Spectroscopy pre-treatment
measure: MRI Spectroscopy
timeFrame: MRI Spectroscopy one week after treatment
measure: MRI Spectroscopy
timeFrame: MRI Spectroscopy six month after treatment
measure: MRI Resting State
timeFrame: MRI resting state pre-treatment
measure: MRI Resting State
timeFrame: MRI resting state one week after treatment
measure: MRI Resting State
timeFrame: MRI resting state six month after treatment
measure: MRI Diffusion weighted images
timeFrame: MRI DSI pre-treatment
measure: MRI Diffusion weighted images
timeFrame: MRI DSI one week after treatment
measure: MRI Diffusion weighted images
timeFrame: MRI DSI six month after treatment
measure: Electroencephalography (EEG) resting state
timeFrame: EEG resting state pre-treatment
measure: Electroencephalography (EEG) resting state
timeFrame: EEG resting state one week after treatment
measure: Electroencephalography (EEG) resting state
timeFrame: EEG resting state six month after treatment
measure: EEG auditory
timeFrame: EEG Auditory pre-treatment
measure: EEG auditory
timeFrame: EEG Auditory one week after treatment
measure: EEG auditory
timeFrame: EEG Auditory six month after treatment
measure: EEG visual
timeFrame: EEG Visual pre-treatment
measure: EEG visual
timeFrame: EEG Visual one week after treatment
measure: EEG visual
timeFrame: EEG Visual six month after treatment
Secondary outcomes:
measure: Behavior Rating Inventory of Executive Function (BRIEF) questionnaire
timeFrame: BRIEF pre-treatment
measure: Behavior Rating Inventory of Executive Function (BRIEF) questionnaire
timeFrame: BRIEF one week after treatment
measure: Behavior Rating Inventory of Executive Function (BRIEF) questionnaire
timeFrame: BRIEF six month after treatment
Other outcomes:
measure: Sensory-motor conflict 1
timeFrame: Synchrony condition pre-treatment
measure: Sensory-motor conflict 1
timeFrame: Synchrony condition one week after treatment
measure: Sensory-motor conflict 1
timeFrame: Synchrony condition six month after treatment
measure: Sensory-motor conflict 2
timeFrame: Asynchrony condition pre-treatment
measure: Sensory-motor conflict 2
timeFrame: Asynchrony condition one week after treatment
measure: Sensory-motor conflict 2
timeFrame: Asynchrony condition six month after treatment
Locations:
city: Geneva
country: Switzerland
facility: Developmental imaging and psychopathology lab
Study officials:
affiliation: University of Geneva, faculty of medicine
name: Stephan Eliez, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Latreche C, Maeder J, Mancini V, Schneider M, Eliez S. Effects of risperidone on psychotic symptoms and cognitive functions in 22q11.2 deletion syndrome: Results from a clinical trial. Front Psychiatry. 2022 Oct 26;13:972420. doi: 10.3389/fpsyt.2022.972420. eCollection 2022.