Frontiers in Psychiatry (May 2024)
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
- María Alemany-Navarro,
- María Alemany-Navarro,
- María Alemany-Navarro,
- Bianca Sánchez-Barbero,
- Bianca Sánchez-Barbero,
- Pablo Reguera-Pozuelo,
- Pablo Reguera-Pozuelo,
- Laura Altea-Manzano,
- Laura Altea-Manzano,
- Ana Gómez-Garrido,
- Ana Gómez-Garrido,
- Idalino Rocha-González,
- Idalino Rocha-González,
- Nathalia Garrido-Torres,
- Nathalia Garrido-Torres,
- Nathalia Garrido-Torres,
- Miguel Ruiz-Veguilla,
- Miguel Ruiz-Veguilla,
- Miguel Ruiz-Veguilla,
- Miguel Ruiz-Veguilla,
- Susana García-Cerro,
- Susana García-Cerro,
- Susana García-Cerro,
- Clara M. Rosso-Fernández,
- José María Villagrán-Moreno,
- José María Villagrán-Moreno,
- José María Villagrán-Moreno,
- José María Villagrán-Moreno,
- Fernando Sarramea,
- Jorge Cervilla-Ballesteros,
- Jorge Cervilla-Ballesteros,
- Rafael Martínez-Leal,
- Rafael Martínez-Leal,
- Rafael Martínez-Leal,
- Fermín Mayoral-Cleries,
- CLOZ-AID Group,
- Benedicto Crespo-Facorro,
- Benedicto Crespo-Facorro,
- Benedicto Crespo-Facorro,
- Benedicto Crespo-Facorro,
- Samuel Romero Guillena,
- Álvaro López Díaz,
- María Dolores Romero Lemos,
- María Conde Rivas,
- Ana Rubio García,
- Manuel Canal Rivero,
- Rubén Catalán Barragán,
- Irene Pans,
- María Luisa Gutierrez,
- Eduardo García Ramos-García,
- Ana Vilches,
- Beatriz Oda Plasencia,
- Ramón Terrón,
- Cristina Valdera,
- Manuela Rey,
- Demetrio Mármol,
- Cristina Esteban,
- Matilde Castaño,
- Juan Pedro Alcón,
- Nicolás Vucinovich,
- Luis R. Capitán,
- Cándido García,
- Matilde Blanco,
- Álvaro J. Palma,
- Susana Herrera Caballero,
- Asunta Torres Laborde,
- Rocío Torrecilla Olavarrieta,
- Melquíades Leon Macías,
- Blanca García Montañes,
- Juan Luis Prados Ojeda,
- José Ángel Alcalá Partera,
- Rafael Manuel Gordillo Urbano,
- Laura Carrión Expósito,
- Cristina Gómez Moreno,
- Pablo Glez Domenech,
- José Eduardo Muñoz Negro,
- Ángeles Torres Prieto,
- Annabel Folch Mas,
- Juan José Mora Mesa,
- Rosa Mz Galindo San Valentín,
- Carlos Peña Salazar,
- Ana Isabel Domínguez Panchón,
- Cristina Irirte Iturria,
- Paula Muñoz Hermoso,
- David Gil Sanz,
- Manuel Calvo Muñoz,
- Georgia Denisa Simon,
- Elena Rodríguez Cano,
- Edith Pomarol Clotet
Affiliations
- María Alemany-Navarro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- María Alemany-Navarro
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
- María Alemany-Navarro
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Bianca Sánchez-Barbero
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Bianca Sánchez-Barbero
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Pablo Reguera-Pozuelo
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Pablo Reguera-Pozuelo
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
- Laura Altea-Manzano
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Laura Altea-Manzano
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Ana Gómez-Garrido
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Ana Gómez-Garrido
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Idalino Rocha-González
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Idalino Rocha-González
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Nathalia Garrido-Torres
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Nathalia Garrido-Torres
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Nathalia Garrido-Torres
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
- Miguel Ruiz-Veguilla
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Miguel Ruiz-Veguilla
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Miguel Ruiz-Veguilla
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
- Miguel Ruiz-Veguilla
- Department of Psychiatry, Faculty of Medicine, University of Seville, Seville, Spain
- Susana García-Cerro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Susana García-Cerro
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
- Susana García-Cerro
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Clara M. Rosso-Fernández
- Clinical Research and Clinical Trials Unit (CTU), Virgen del Rocío Hospital, Seville, Spain
- José María Villagrán-Moreno
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- José María Villagrán-Moreno
- Mental Health Unit, Área de Gestión Sanitaria Jerez, Costa Noroeste y Sierra de Cádiz, Cádiz, Spain
- José María Villagrán-Moreno
- Neurosciences Department, University of Cádiz, Cádiz, Spain
- José María Villagrán-Moreno
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
- Fernando Sarramea
- 0Área de Gestión Sanitaria Córdoba, Córdoba, Spain
- Jorge Cervilla-Ballesteros
- 1Hospital Universitario San Cecilio, Granada, Spain
- Jorge Cervilla-Ballesteros
- 2Psychiatry Department, University of Granada, Granada, Spain
- Rafael Martínez-Leal
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Rafael Martínez-Leal
- 3Fundació Villablanca, Unidad de Investigación en Discapacidad Intelectual y Trastornos del Desarrollo (UNIVIDD), Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- Rafael Martínez-Leal
- 4Psychology Department, Universitat Rovira i Virgili, Tarragona, Spain
- Fermín Mayoral-Cleries
- 5Psychiatry Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
- CLOZ-AID Group
- Benedicto Crespo-Facorro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Benedicto Crespo-Facorro
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Benedicto Crespo-Facorro
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
- Benedicto Crespo-Facorro
- Department of Psychiatry, Faculty of Medicine, University of Seville, Seville, Spain
- Samuel Romero Guillena
- Álvaro López Díaz
- María Dolores Romero Lemos
- María Conde Rivas
- Ana Rubio García
- Manuel Canal Rivero
- Rubén Catalán Barragán
- Irene Pans
- María Luisa Gutierrez
- Eduardo García Ramos-García
- Ana Vilches
- Beatriz Oda Plasencia
- Ramón Terrón
- Cristina Valdera
- Manuela Rey
- Demetrio Mármol
- Cristina Esteban
- Matilde Castaño
- Juan Pedro Alcón
- Nicolás Vucinovich
- Luis R. Capitán
- Cándido García
- Matilde Blanco
- Álvaro J. Palma
- Susana Herrera Caballero
- Asunta Torres Laborde
- Rocío Torrecilla Olavarrieta
- Melquíades Leon Macías
- Blanca García Montañes
- Juan Luis Prados Ojeda
- José Ángel Alcalá Partera
- Rafael Manuel Gordillo Urbano
- Laura Carrión Expósito
- Cristina Gómez Moreno
- Pablo Glez Domenech
- José Eduardo Muñoz Negro
- Ángeles Torres Prieto
- Annabel Folch Mas
- Juan José Mora Mesa
- Rosa Mz Galindo San Valentín
- Carlos Peña Salazar
- Ana Isabel Domínguez Panchón
- Cristina Irirte Iturria
- Paula Muñoz Hermoso
- David Gil Sanz
- Manuel Calvo Muñoz
- Georgia Denisa Simon
- Elena Rodríguez Cano
- Edith Pomarol Clotet
- DOI
- https://doi.org/10.3389/fpsyt.2024.1400621
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundIntellectual 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.MethodsA 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.DiscussionThe 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 registrationClinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.
Keywords