Computer-assisted Risk Evaluation in the Early Detection of Psychotic Disorders

Study Overview
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Brief Summary
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Multicenter randomized controlled trial (RCT) with artificial intelligence (AI)-staged early diagnostics and risk-adapted treatment (RAB) as interventional treatment arm and treatment-as-usual (TAU) as control treatment arm for patients with an increased clinical risk for psychosis.

Detailed Description
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The study is a Investigator Initiated Trial (IIT)/Other clinical trial of a class 2a medical device according to article 82 medical devices regulation of the European Union. The aim of risk-adapted treatment (RAB) arm is to reduce the number of patients with an increased clinical risk for psychosis (ICD-10: schizophrenic disorders F2x.x, affective disorders F3x.3) to actually develop a manifest psychosis. Patients assigned to the active treatment arm will receive additional in-depth clinical diagnostics including neuropsychological testing. The AI-supported algorithm pronia.ai uses information from both the individual patient data of the specialized routine diagnostics as well as from in-depth clinical diagnostics. There are two predictions, an individual quantitative assessment of the individual risk of transition to psychosis and the individual prognosis with regard to the level of psychosocial functioning 12 months after inclusion in the study. The therapists and patients receive a non-binding risk profile from the AI-based recommendation to adjust the treatment intensity from 16 to 24 sessions over a period of six months. The cognitive behavioral therapy-based manual Integrated Preventive Psychological Preventive Psychological Intervention (IPPI) manual is used. In the treatment-as-usual arm (TAU),the patients receive referral back to the previous care system; further treatment (and additional diagnostics, if necessary) is left to the referring primary care providers.

Official Title
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Computer-assisted Risk Evaluation in the Early Detection of Psychotic Disorders

Conditions
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Psychotic Disorders, Prevention

Intervention / Treatment
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* Device: pronia.ai medical device for high risk psychosis prognosis
* Other: Treatment-as-usual (TAU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The increased risk of psychosis includes either a symptomatic ultra high-risk stage of the Structured Interview for Psychosis-Risk Syndromes or the Cognitive Disturbances risk criterion of the Schizophrenia Proneness Instrument - Children and Youth and Adult versions ages 16 to 40 Presence of a written Exclusion Criteria: manifest psychosis (ICD-10 F2x.x, F3x.3) according to the definition of the Structured Interview for Psychosis-Risk Syndromes . Lack of capacity to give consent (the patient lacks the capacity to consent if the individual case with regard to the specific treatment measure is excluded. Only when the physician has concrete indications that that the patient's capacity to consent may be lacking, he may and must must examine it. Mental disorders (e.g. delirium, dementia, psychosis, mania, depression) or cognitive impairments can have an influence on the capacity to consent. Indications for doubts of a ability to give informed consent exist if the physician has the impression that the patient is not able to understand the provided patient information and is not able to reproduce essential information about the study in his or her own words and is not aware of the possible consequences of the proposed measures Severe suicidality during the recruitment phase (CDSS items 8 ≥2) A current or past neurological disease of the brain. a current or past known somatic disease that potentially affects the structure or function of the brain Antipsychotic medication for >30 days (cumulative number of days). At or above the minimum dose for a psychotic first episode according to the the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) S3 guidelines an antipsychotic medication in the 3 months prior to baseline. (regardless of the length of time taken) at or above the minimum dose for a psychotic first episode according to the DGPPN S3-guidelines An inadequate level of hearing for neurocognitive testing a current or past head trauma with unconsciousness (>5 min.; a current or past alcohol dependence (ICD-10 F10.x) A current polytoxicomania (multiple substance dependence) or polytoxicomania in the past 6 months (ICD-10 F19.x) Presence of medical reasons that contraindicate performance of an MRI Insufficient language skills to understand the indication and the purpose of the intended examinations and interventions stationary accommodation against the patient's will

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The aim of risk-adapted treatment (RAB) arm is to reduce the number of patients with an increased clinical risk for psychosis (ICD-10: schizophrenic disorders F2x.x, affective disorders F3x.3) to actually develop a manifest psychosis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CARE interventional treatment<br>AI-computerassisted prognosis of high risk psychosis profile and adapted study-specific therapy taking place in early-recognition centers. | Device: pronia.ai medical device for high risk psychosis prognosis<br>* In addition to the computer-assisted prognosis of risk for reaching a psychosis, all patients assigned to the active treatment arm will receive additional in-depth clinical diagnostics including neuropsychological testing. Adapted psychological treatment will be offered consisting of 16 to 24 sessions over a period of six months.<br>|
| Active Comparator: Standard of Care Control arm<br>Treatment as usual (TAU) patient will receive their usual treatment from their local physicians and therapeutic personnel. | Other: Treatment-as-usual (TAU)<br>* Referral back to the previous care system. Further treatment is left to the referring primary care providers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structured Interview for Psychosis-Risk Syndromes (SIPS) | Presence of psychotic syndrome (POPS) criteria as modified according to the PRONIA study, resulting in a score of 0= no psychosis or 1= psychosis | 12-month after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Internalized Stigma of Mental Illness Scale (ISMI) | Consisting of 5-subscales, comprising of 29 items in total using response formats varying from 4-point Likert scales (1='not at all', 4='very often') to 5-point Likert scales (1='never', 5='very often'), assessing self-stigma in terms of alienation, adoption of stereotypes, experiences of discrimination, social withdrawal and stigma resistance. | 12-month after inclusion | 
| Stigma-Stress-Scale | two dimensions are assessed, 8 items are rated on a 5-point Likert-scale from strongly disagree to totally agree, capturing self-assessed-stigma stress. | 12-month after inclusion | 
| Self-Identification of Mental Illness Scale (SELF-I) | 5-point Likert-scale ranging from 1 = not true at all to 5 =  is completely true, capturing the degree of self-identification with mental illnesses. | 12-month after inclusion | 
| Coming-Out with Mental Illness Scale (COMIS) | consisting of two subscales with 7 and 14 items, each with 7-step Likert-scale ranging from 1 = do not agree at all to 7 =  totally agree, capturing a potential change of strategies for dealing with mental illness. | 12-month after inclusion | 
| Secrecy and disclosure-related distress - scale | 7-point single-item-scale ranging from 1 =  not at all to 7 = very much, measuring the degree of subjective stress. | 12-month after inclusion | 
| Psychosis own health-concern single score | 5-point Likert-scale ranging from 1 = not at all to 5 = strong, capturing the degree of self-concern in terms of getting a psychosis one day. | 12-month after inclusion | 
| Numeracy Scale | A single score from 0 to 100% indicating the patient self-estimated amount of belief in risk for developing psychosis within the next 12 months. | 12-month after inclusion | 
| Coping (Ten-Flex) | Patient self-estimation of likelihood for developing psychosis given on a visual analogue scale (VAS) indicating I will not develop psychosis in the next 12 months on the left side of the scale up to I will definitely develop psychosis in the next 12 months on the right side of the scale. | 12-month after inclusion | 
| Risk Perception Scale | A score from 1 =no risk to 7 = absolutely certain indicating the risk for developing psychosis. | 12-month after inclusion | 
| Risk Recall Scale | A score from 1 = much lower to 5 much higher indicating the risk for developing psychosis compared to a healthy peer. | 12-month after inclusion | 
| Health-related quality of life (EQ-5D) | patient questionnaire consisting of two sub-scores. a) score from 0-10 whereas a higher score indicates greater impairment; b) score from 0-100 whereas a higher score indicates better current health status to measure the quality of Life. | 12-month after inclusion | 
| Brief Multidimensional Life Satisfaction Scale (BMLSS) | Score from 0-126, a higher score indicates a higher amount of satisfaction. | 12-month after inclusion | 
| Client Sociodemographic and Service Receipt Inventory (CSSRI-EU) | Changes in service use are measured with a semi-structured interview to assess social and demographic data, accommodation data, detailed information regarding treatment, professional visits and social and health service utilization for estimating healthcare costs. Additionally, the CSSRI systematically records the use of psychiatric, medical, psycho-social and rehabilitative health services (direct costs) and productivity losses (indirect costs) and therefore completely covers the costs of the disease from an economic perspective. | 12-month after inclusion | 
| Patient Satisfaction Questionnaire (ZUF-8) | 8 Items with a total score of 8-32, ranging from 4 = very satisfied to 1=fairly satisfied whereas a higher score indicates higher patient satisfaction. | 12-month after inclusion | 
| Social and occupational assessment scale SOFAS | Scores from 0-100, a higher score indicates better social functioning. | 12-month after inclusion | 
| Global Functioning Social Scale (GF:S) | Scores from 1-10, a higher score indicates better global functioning | 12-month after inclusion | 
| Global Functioning Role Scale (GF:R) | Scores from 1-10, a higher score indicates better functioning | 12-month after inclusion | 
| Secrecy-Symptoms Scale | Five questions (either yes or no) asking who the patient has told about the risk for developing psychosis | 12-month after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychosis-Risk Syndromes, high-risk, Cognitive Disturbances, Artificial Intelligence