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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Psychotic Disorders; Prevention
• Intervention / Treatment: Device: "pronia.ai" medical device for high risk psychosis prognosis; Other: Treatment-as-usual (TAU)

Detailed Description

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 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.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 10967
    • Vivantes Klinikum Am Urban
  • Hamburg, Germany, 20246
    • Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Hamburg-Eppendorf {UKE)
  • Baden-Württemberg
    • Konstanz, Baden-Württemberg, Germany, 78479
      • ZfP Reichenau - Akademisches Lehrkrankenhaus Universität Konstanz
    • Mannheim, Baden-Württemberg, Germany, 68159
      • Zentralinstitut für Seelische Gesundheit
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Klinik für Psychiatrie und Psychotherapie Universität Tübingen
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Bezirkskrankenhaus Augsburg, Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Universität Augsburg
  • Bayern
    • München, Bayern, Germany, 80336
      • Klinikum der Ludwig-Maximilians-Universität München
    • Würzburg, Bayern, Germany, 97080
      • Zentrum für psychische Gesundheit, U11iversitätsklinikum Würzburg
  • NRW
    • Aachen, NRW, Germany, 52074
      • Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Universitätsklinikum Aachen, RWTH Universität Aachen
    • Bochum, NRW, Germany, 44791
      • LWL-Universitätsklinikum Bochum der Ruhr--Universität Bochum, Klinik für Psychiatrie, Psychotherapie und Präventivmedizin
    • Bonn, NRW, Germany, 53111
      • KJPP LVR-Klinik Bonn
    • Bonn, NRW, Germany, 53127
      • Universitätsklinikum Bonn Klinik für Psychiatrie und Psychotherapie
    • Düsseldorf, NRW, Germany, 40629
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie Heinrich-Heine-Universität Düsseldorf
    • Köln, NRW, Germany, 50931
      • Uniklinik Köln, Klinik und Poliklin-ik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters
    • Münster, NRW, Germany, 48149
      • Institut für Translationale Psychiatrie
  • Rheinland-Pfalz
    • Alzey, Rheinland-Pfalz, Germany, 55232
      • Rheinhessen Fachklinik Alzey
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • UKD Dresden, Klinik und Poliklinik für Psychiatrie und Psychotherapie
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • Otto-von-Guericke- Universität Magdeburg
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Zentrum für Integrative Psychiatrie Kiel
    • Lübeck, Schleswig-Holstein, Germany, 23554
      • Zentrum für Integrative Psychiatrie (ZIP) und Fachklinik für Junges Leben (JuLe) Kinder- und Jugendpsychiatrie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 informed consent from the patient and, if applicable, the legal guardian.

Exclusion Criteria:

• manifest psychosis according to the definition of the Structured Interview for Psychosis-Risk Syndromes (according to the PRONIA-study) (At least one P-syndrome with a rating of 6 on a daily frequency and for a period of more than one week)
• 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 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 in the indication treatment of psychotic symptoms for >30 days (cumulative number of days) at or above the starting dose for psychosis according to the current German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) S3 guidelines.
• an antipsychotic medication in the indication treatment of psychotic symptoms in the 3 months prior to the initial examination (regardless of the duration of use) at or above the starting dose for psychosis according to the current 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CARE interventional treatment; 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; 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.
Active Comparator: Standard of Care Control arm; Treatment as usual (TAU) patient will receive their usual treatment from their local physicians and therapeutic personnel.	Other: Treatment-as-usual (TAU); Referral back to the previous care system. Further treatment is left to the referring primary care providers.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Eva Meisenzahl-Lechner, Prof., Klinik und Poliklinik für Psychiatrie und Psychotherapie LVR-Klinikum Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Artificial Intelligence; high-risk; Psychosis-Risk Syndromes; Cognitive Disturbances
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: HeinrichHeine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No