Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial

Front Psychiatry. 2024 May 14:15:1400621. doi: 10.3389/fpsyt.2024.1400621. eCollection 2024.

Abstract

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field.

Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them.

Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials.

Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Keywords: antipsychotics; clozapine; effectiveness; intellectual disability; resistant psychosis.

Associated data

  • ClinicalTrials.gov/NCT04529226

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study has been funded by Instituto de Salud Carlos III through the project "ICI19/00026" (Co-funded by European Regional Development Fund/European Social Fund; “A way to make Europe”/"Investing in your future"). Prof. BC-F has received unrestricted research funding from Carlos III Health Institute, MINECO, Gobierno de Cantabria, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), from the 7th European Union Framework Program and Lundbeck. He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen Cilag, Rovi, Angelini, Boehringer, Mylan, Lundbeck, and Otsuka Pharmaceuticals. MA-N was supported by a Juan de la Cierva contract (FJC2021-047538-I).