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

NCT ID: NCT04639960

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-29

Study Completion Date

2021-05-01

Brief Summary

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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

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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).

Conditions

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22q11.2 Deletion Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

double blind placebo design
Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
the pharmacy has prepared the randomization. group membership will be revealed at the end of the study.

Study Groups

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Risperidone

Group Type EXPERIMENTAL

Risperdal

Intervention Type DRUG

Twelve weeks of treatment with a gradual increase of dosage over one week and a gradual decrease over two weeks.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Twelve weeks of placebo treatment.

Interventions

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Risperdal

Twelve weeks of treatment with a gradual increase of dosage over one week and a gradual decrease over two weeks.

Intervention Type DRUG

Placebo

Twelve weeks of placebo treatment.

Intervention Type DRUG

Other Intervention Names

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risperidone

Eligibility Criteria

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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.
Minimum Eligible Age

11 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Geneva, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Stephan Eliez

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stephan Eliez, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Geneva, faculty of medicine

Locations

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Developmental imaging and psychopathology lab

Geneva, , Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type DERIVED
PMID: 36386982 (View on PubMed)

Other Identifiers

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PB_201601540

Identifier Type: -

Identifier Source: org_study_id