Clinical trial NCT06423651: Benefits of Combining MCT With CR in the Recovery of Patients With Psychotic Spectrum Disorders
Official title: Benefits of Combining Metacognitive Training (MCT) With Cognitive Remediation (CR) in the Recovery of Patients With Psychotic Spectrum Disorders (CR+MCTp)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia
Schizophreniform Disorders
Delusional Disorder
Brief Psychotic Disorder
Schizoaffective Disorder
Schizophrenia Spectrum and Other Psychotic Disorders
Keywords: Metacognitive Training
MCT
Cognitive Remediation
Psychotic disorder
Psychosis
Cognitive functions
Cognitive biases
Neurocognitive improvement
Lead sponsor: Universitat Autonoma de Barcelona
Sponsor class: OTHER
Collaborators: name: Parc Sanitari Sant Joan de Déu
name: Consorci Sanitari de Terrassa
name: Hospital de Mataró
name: Centre d'Higiene Mental Les Corts
name: Fundació Els 3 Turons
name: Hospital San Carlos, Madrid
name: Andaluz Health Service
name: Institut d'Assistència Sanitària
name: Ministerio de Ciencia, Innovación y Universidades
name: Hospital Son Espases
name: Parc Taulí Hospital Universitari
name: Servicio Cántabro de Salud
First posted: 2024-05-21
Enrollment: 160
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a randomized clinical trial in which one group will receive combined REHACOP + MCT therapy and another group will receive therapy with MCT alone. The metacognitive treatment will have the same characteristics in the two treatment conditions. Randomisation of the patients for receiving one of the two treatments will be carried out using a random number list based on the order of access to their reference centre. The evaluator will be blinded to the treatment group to which the patient assessed belongs.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the efficacy of combined REHACOP + MCT alone in persons with nonaffective psychotic disorder in terms of recovery. The main questions it aims to answer are:

* Does combined REHACOP + MCT therapy increase the clinical recovery in persons with nonaffective psychotic disorder (compared to MCT alone)?
* What is the impact of combined REHACOP + MCT therapy compared to MCT therapy alone on personal/psychological recovery, cognitive biases, and social cognition, taking gender differences into account?
* What is the durability of the effects of combined REHACOP + MCT therapy compared to MCT therapy alone on clinical recovery, personal recovery, cognitive biases, and social cognition in the long term?

Researchers will compare REHACOP+MCT therapy to MCT alone to see if there are differences in personal/psychological recovery.

Participants will:

* Participate in Metacognitive Training or in combined REHACOP + Metacognitive training therapy.
* Do 8 weekly sessions of 45-60 minutes (MCT group).
* Do 12 weekly sessions of 45-60 minutes (RECHACOP+MCT group).
* Visit the clinic for checkups and tests.
* Answer self-administered tests.

Detailed description: This project is aimed at responding to one of the Challenges of the Spanish Strategy for Science, Technology and Innovation, specifically Challenge 1: Health, demographic change and well-being. One of the work areas that are located within this challenge is the Clinical and Translational Research based on the evidence of scientific and technological knowledge.The present proposal is clearly within the framework of clinical-translational investigation, since most of the entities participating attend persons with psychotic disorders, thereby ensuring the translation of investigation to the clinical setting. In addition, this project includes investigators with wide experience in psychological interventions in the target population and with previous experience in investigation in this area. Lastly, it is of note that the benefits of this investigation are not only of a scientific nature but also involve clinical investigation with a direct repercussion on improvement in the health care of people with psychotic disorders, enabling the design of new strategies of psychological interventions. Besides, the present proposal is aimed at responding to the challenges of our society, contributing to covering the needs of persons with psychotic disorder as well as developing the most effective therapeutic strategies to improve aspects related to clinical and personal recovery. Specifically, this project will allow making changes that will improve the quality of health care to the target population incorporating the combinated use of scientifically proven therapeutic strategies to health care services. In short, this project aims to promote innovation in the provision of mental health services, being the starting point in analyzing the efficacy of combined psychological therapies versus monotherapies address to improve of metacognitive processes.

- General and specific objectives. General objective: Compare the efficacy of combined REHACOP + MCT therapy vs. MCT alone in persons with nonaffective psychotic disorder in terms of recovery.

Specific objectives:

* Evaluate the effects of combined REHACOP + MCT therapy vs. MCT alone on clinical recovery (clinical remission and functional recovery, the latter understood in terms of cognitive, occupational and social functioning).
* Evaluate the effects of combined REHACOP + MCT therapy vs. MCT alone on personal/psychological recovery.
* Evaluate the effects of combined REHACOP + MCT therapy vs. MCT alone on cognitive biases and social cognition.
* Evaluate the effects of combined REHACOP + MCT therapy vs. MCT alone according to gender.
* Evaluate the effects of combined REHACOP + MCT therapy vs. MCT alone according to self-esteem, quality of life and stigma.
* Evaluate the maintenance of the effects of combined REHACOP + MCT therapy vs. MCT alone on clinical recovery, personal recovery, cognitive biases and social cognition in the long term.
* Methodology

Design:

This will be a randomised clinical trial in which one group will receive combined REHACOP + MCT therapy and another group will receive therapy with MCT alone. The metacognitive treatment will have the same characteristics in the two treatment conditions. Randomisation of the patients for receiving one of the two treatments will be carried out using a random number list based on the order of access to their reference centre. The evaluator will be blinded to the treatment group to which the patient assessed belongs.

Study subjects: The sample will be made up of people with non-affective psychotic disorder who are attended in any of the centres participating in the study which belong to the following entities:Consorci Sanitari de Terrassa; Hospital de Mataró; Instituto de Investigación Biomédica de Gerona (IdIBG); Parc Sanitari Sant Joan de Déu; Asociación Centro de Higiene Mental Les Corts; Hospital Sierrallana-Tres Mares; and UGC Salud Mental de Jaén.

Sample size: Considering that the investigators have no preliminary data on our principal objective in relation to clinical and personal recovery, the score obtained in the global assessment of functioning (GAF) at follow-up will be taken as a measure of outcome, since it is implicated in both clinical and functional recovery. The investigators used the data published in the article by Ochoa et al. (2017) in order to calculate the required sample size for this study. In this article, a difference of means of 5.73 points (SD=11.51) is obtained in the GAF scale from baseline and the follow-up at 6 months after the intervention. With these data, the necessary sample size has been estimated with an alpha of 0.05 and a power of 0.8. Taking into account 20% of possible losses to follow-up, the sample size has been calculated as 160 cases, 80 in each experimental arm (REHACOP + MCT vs. MCT). In this way, taking into account that the intervention groups will be carried out in the health care centers of 7 different entities each will have to recruit 24 patients, 12 for each experimental condition.

Data collection: the professional who makes the referral of the patients to the study will be responsible for reviewing fulfillment of the inclusion and exclusion criteria. Patients fulfilling the inclusion criteria will receive an explanation of the study and if they accept to participate, they must provide signed informed consent. The evaluation will be carried out at 3 time points: T0 (basal assessment, prior to initiation of treatment). All the previously described scales will be administered; T1 (post-treatment evaluation), all the scales will be administered and, in addition, the satisfaction perceived with the interventions received will be evaluated; T2 (follow-up evaluation ) at 6 months after completing the intervention all the scales will again be administered. In addition, the number of relapses and hospitalizations during the time interval will be registered. Assessment of the PANSS and GAF should take into account the temporal criterium mentioned in the section of 'Outcomes'. A contingency plan will be considered in the event that difficulties are detected in carrying out any of the phases of the study due to external causes, such as the continuity of the COVID-19 pandemic. This plan will consist of the implementation of interventions and evaluations making use of new technologies. All the centers already have the adequate infrastructure to carry out the project under these conditions.

Data analysis: Firstly, the two groups will be compared with the aim of verifying that there are no significant differences at baseline to confirm that they are comparable after randomization. Comparisons of means for independent samples will be carried out using the Student's t-test for continuous variables and the Chi-square test for categorical variables. The variables of the principal analysis will be the difference between the scores of the two groups (REHACOP+MCT and MCT) in the scores of the scales assessing clinical and personal/psychological recovery. The secondary results will be the differences in other assessments of social functioning, cognitive biases, and social cognition on comparing the two experimental conditions. Changes in the scores of these scales will be analyzed using regression methods for repeated measures, with the post-treatment score of the scales as the dependent variable and the basal score and the REHACOP+MCT group as the co-variables. Temporal stability of the results at 6 months will be assessed using the follow-up score as the dependent variable and evaluating how this affects the basal score, post treatment and the experimental condition. The statistical analyses will be performed according to intention to treat (ITT) without imputing the lost values. Gender, antipsychotic medication, and disease evolution time will be considered as control variables.

Limitations:

One of the limitations of this clinical trial might be the loss to follow-up. To compensate for these losses the sample size will be increased by 20%. It is expected that the losses to follow-up will be similar in the two groups. Otherwise, this variable will be considered as an indicator of the acceptability of treatment.

- Ethical considerations: All the people who participate in the trial will sign the informed consent that takes into account the Declaration of Helsinki and the Organic Law 03/2018 of December 5. In the cases of minors informed consent will be signed by the legal guardians The project will be evaluated by each of the Ethics Committees of the participating centers.

Participants will be informed that the data obtained will only be used for purposes related to the investigation and data confidentiality will be guaranteed according to the provisions of Organic Law 03/2018, of December 5 and Regulation (EU) 2016/679 of the European Parliament and of the Council, of April 27, 2016 and data protection (RGPD). The data management plan generated by the project, all information will be stored and managed in a secure and confidential manner, in accordance with the provisions of Organic Law 03/2018. In order to scrupulously respect the current legislation, the following measures will be taken:

1. Personal data will be pseudonymized. The identifying data are separated from the variables studied in the study. Therefore, a technical and functional separation will be made between the research team and those who perform the pseudonymization and retain the information that allows the reidentification of the participant. Pseudonymized data will only be accessible to the research team when: i) there is an express commitment to confidentiality and no re-identification activity, and ii) specific security measures are taken to prevent re-identification and access to unauthorized personal.
2. The person receiving the informed consent and custody will be different from the person who will process the data, or if this is not possible, the entire research team will sign an express commitment of confidentiality not to carry out re-identification activities. The signed informed consents will be kept under lock and key and out of the reach of the research team in a generic sense.

Eligibility criteria: Inclusion Criteria:

* Presence of one of the e following diagnostics according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5): schizophrenia, schizophreniform disorder, delusional disorder, brief psychotic disorder, schizoaffective disorder, and non specified schizophrenia spectrum disorder and other psychotic disorders.
* Be in a stable clinical phase (without psychiatric hospitalization in the last 3 months).
* Have good adherence to pharmacological treatment.
* T-score \< 40 in any cognitive outcome measured by TAVEC, CPT-IP, TMT, Stroop, WSCT, FAS and WAIS (Vocabulary, Digit Forward, Digit Backwards and Digit Symbol Coding.
* Willing to participate in the study expressed by providing signed informed consent.

Exclusion Criteria:

* Presence of traumatic brain lesion, dementia or intellectual discapacity (IQ \<70).
* Positive and Negative Syndrome Scale (PANSS) score \>= 5 in hostility and lack of cooperation and \>= 6 in suspiciousness.
* Presence of an additional diagnosis of severe disorder related to substances.
* Having participated in a CR and/or MCT intervention in the year prior to incorporation into the study.

Primary outcomes:
measure: CLINICAL RECOVERY
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: FUNCTIONAL RECOVERY
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
Secondary outcomes:
measure: Assesment instruments
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Social Cognition. Recognition of emotion
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Social Cognition. Hinting Task (Corcoran et al., 1995; Gil et al., 2012)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Social Cognition. Internal, Personal and Situational Attributions Questionnaire (IPSAQ) (Kinderman & Bentall, 1996; Diez-Alegría, 2006)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Ball task (Dudley et al.,1997).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Cognitive Bias Questionnaire (CBQ) (Peters et al., 2013; Gutiérrez-Zotes, in press).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Beck Cognitive Insight Scale (BCIS) (Beck et al., 2004; Guitiérrez-Zotes et al., 2012).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Social Functioning Scale (SFS) (Birchwood et al., 1990; Torres and Olivares, 2000).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Cognitive functioning.
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Global Assessment Functioning (GAF) (Endicott et al., 1976).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Positive and negative syndrome scale (PANSS) (Kay et al., 1987; Peralta and Cuesta, 1995).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Continuous Performance Test II (CPT-II) (Conners, 2000); Trail Making Test (TMT) (Reitan,1993).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Rey Auditory Verbal Learning Test (RAVLT) (Rey, 1964)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Wisconsin Card Sorting Test (WCST) (Bergs et al., 1948)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Trail Making Test (TMT-B) (Reitan, 1993)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Stroop Color and Word Test (Stroop, 1935)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Trail Making Test (TMT-A) (Reintan, 1993)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Controlled Oral Word Association Test (COWAT) (Benton&Hamsher, 1976)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Letter-number sequencing (Wechsler Adult Intelligence Scale [WAIS]) (Weschler, 1999)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: The Stages of Recovery Instrument (STORI) (Andresen et al., 2006; Lemos et al., 2015)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: WHO Quality of Life-BREF 26. (WHOQOL-BREF) (Üstun et al., 1988; Vázquez-Barquero et al., 2000).
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: World Health Organization Disability Assessment Schedule (WHO-DAS-II) (Üstun et al., 1988; Vázquez-Barquero et al., 2000)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Internalized Stigma of Mental Illness Scale (ISMI) (Ritsher, Otilingama, Grajalesa, 2003)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
measure: Rosenberg self-esteem scale (RSES) (Rosenberg et al., 1965; Atienza, Balaguer & Moreno, 2000)
timeFrame: It will be administered 1 time before de treatment, 1 time after finishing the treatment and 1 time after 6 months completing the intervention.
Other outcomes:
Locations:
city: Cerdanyola Del Vallès
country: Spain
facility: Universitat Autonoma de Barcelona
state: Barcelona
Study officials:
affiliation: Universitat Autonoma de Barcelona
name: Ana Barajas Velez
role: PRINCIPAL_INVESTIGATOR
References: