PERMEPSY: A Multicentre, Randomized, Double-Blind Proof-of-Concept Trial of Personalised Metacognitive Training for Adults with Psychosis. A Study Protocol.

Maria Lamarca^1,2,3,4*Claudia Requejo^1,2Adrianna Aleksandrowicz⁵Adrien Goncalves⁶Martyna Kreżołek⁵Hanna Gelner⁵Justyna Piwińska⁵Rabea Fischer⁷Merle Schlechte⁷Alvaro Cavieres^8,9Vanessa Acuña^10,8Fabrice Berna⁶Steffen Moritz⁷Caroline König¹¹Łukasz Gawęda⁵Susana Ochoa^1,2,3

• ¹Parc Sanitari Sant Joan de Deu, Sant Boi de Llobregat, Spain
• ²Grup MERITT, Fundació Sant Joan de Déu, Institut de Recerca Sant Joan de Deu, Barcelona, Spain
• ³Centro de Investigacion Biomedica en Red de Salud Mental, Madrid, Spain
• ⁴Departament de Psicologia Clínica i de la Salut, Universitat Autonoma de Barcelona Facultat de Psicologia, Bellaterra, Spain
• ⁵Experimental Psychopathology Lab, Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland
• ⁶Inserm, Les Hopitaux Universitaires de Strasbourg, Strasbourg, France
• ⁷Department of Psychiatry and Psychotherapy, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany
• ⁸Unidad de Trastornos Psicóticos, Hospital Del Salvador de Valparaíso, Valparaíso, Chile
• ⁹Universidad de Valparaiso, Valparaíso, Chile
• ¹⁰Departamento de Psiquiatría, Escuela de Medicina, Facultad de Medicina, Universidad de Valparaiso, Valparaíso, Chile
• ¹¹Soft Computing Research Group at Intelligent Data Science and Artificial Intelligence Research Center, Universitat Politecnica de Catalunya, Barcelona, Spain

Background: While psychological interventions are effective at improving symptoms of psychosis, accessible, cost- and time-efficient treatments remain limited. Personalised medicine has emerged as a promising approach, tailoring interventions to individual needs. Metacognitive Training (MCT), with its established efficacy and adaptable format, is well-suited for personalisation. The PERMEPSY project (Towards a Personalised Medicine Approach to Psychological Treatment for Psychosis) aims to deliver tailored MCT intervention for individuals with psychosis. Methods: PERMEPSY is an international study funded by ERAPerMed (JTC2022) involving five clinical partners (Spain, Germany, France, Poland, Chile) and one technological partner (Spain). The project involves a proof-of-concept clinical trial recruiting 51 participants from each centre for a total of 255 adult participants with psychosis in a prospective study (Registration: NCT06603922, 19-09-2024). The trial will test the efficacy of a Machine Learning (ML)-derived platform at predicting clinical and functional outcomes from baseline scores and compare a personalised MCT (P-MCT) to a classical MCT based on the platform’s predictions. Aims: PERMEPSY seeks to (1) develop and test the predictive power of an algorithm that could support decision-making, and (2) ascertain whether P-MCT is more effective than MCT at improving key symptoms and cognitive impairments associated to psychosis. Results: A harmonised retrospective database enabled the development of a predictive ML algorithm, integrated into an innovative platform. This platform provides clinicians with the information needed to deliver P-MCT. Predictions include changes in positive symptoms (e.g., delusions), insight, self-esteem, and treatment adherence. Discussion: By integrating diverse data types and innovative technology, PERMEPSY addresses the need for personalised, effective treatment in psychosis, aiming to reduce individual and systemic burdens while supporting clinicians in their decision-making.