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Efficiency of a Composite Personalised Care on Functional Outcome in Early Psychosis

Phase 3
Not yet recruiting
Conditions
Psychosis
Interventions
Other: Treatment as usual (TAU)
Behavioral: Cognitive training
Registration Number
NCT05796401
Lead Sponsor
Centre Hospitalier St Anne
Brief Summary

Chronic psychosis, including schizophrenia is now viewed as a progressive disorder where cognitive deficits predate the clinical onset. Early intervention programs improve the general outcome with staged care strategies, supporting the view that the period before and around the first episode of psychosis is a window of opportunity for improving its functional recovery.

Pioneering epigenetic analyses indicate that psychosis onset involves oxidative stress and inflammation suggesting that neuroprotective strategies could limit or even prevent the onset of or the transition into a chronic disorder. Several biological factors associated with the emergence of psychosis can all be rectified by using safe and easily accepted supplements including alterations folate deficiency/hyperhomocysteinemia; redox imbalance and deficit in polyunsaturated fatty acids (PUFA). The prevalence of these anomalies (20-30%) justifies a systematic detection and could guide personalised add-on strategy.

Cognitive remediation improves quality of life (QoL) and functional outcome in patients with chronic psychosis. It would even be more efficacious in the early phase of psychosis by tackling the negative impact of psychosis on education achievement and employment. However, cognitive dysfunctions are often overlooked in patients at ultra-high risk (UHR) for psychosis and patient with a first episode of psychosis (FEP) and cognitive remediation is not always accessible. New technologies can provide us with youth-friendly, non-stigmatising tools, such as applications with cognitive strategies, motivational tools and functioning guidance personalised according to the need of each individual. Patients can have access to it, wherever they live.

Early psychosis can be associated with inflammation, metabolic deficiency, as well as early structural brain anomalies that reflect brain plasticity abilities and could influence the prognosis and response to cognitive training.

The study hypothesis is that promoting neuroplasticity by cognitive training and personalised virtual psychoeducation guidance could attenuate or reverse early cognitive deficits and improve the overall functional outcome in young patients UHR or FEP and that this effect is modulated by individual brain plasticity abilities. The overall objective of PsyCARE_trial is to improve early intervention in psychosis by providing a composite personalised care (CPC) that will enable personalised cognitive training and psychoeducation guidance, adapted to individuals' needs, cognitive abilities and biological background.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
500
Inclusion Criteria
  • Adolescent and young adults, both sexes, aged 15 to 30 years,
  • From Community or academic clinics,
  • Characterised as UHR or FEP according to the first four items of the Comprehensive Assessment of At Risk Mental State (CAARMS) (first subscale for psychosis) [8] during the last 12 months,
  • Informed and written signed consent,
  • Participant with regular health insurance
Exclusion Criteria
  • Severe and unstabilised medical conditions,
  • Insufficient level in reading and/or French language,
  • Current participation in another intervention trial,
  • Enforced hospitalization ,
  • Intellectual Deficiency (i.e. Intelligence Quotient<70), and / or sensorimotor deficits incompatible with the cognitive training,
  • Former treated episode of psychosis, chronic schizophrenia, schizoaffective, or Bipolar disorder,
  • Current severe depression (i.e. MADRS > 34),
  • Receiving therapeutic levels of antipsychotics for more than 12 months,
  • Current medication with benzodiazepine >30 mg per day equivalent diazepam
  • Current daily use of substance of abuse (higher than an average equivalent of daily number of 5 cannabis cigarettes). Current severe substance use disorder except for nicotine (SUD, Diagnostic and Statistical Manual of Mental Disorders version V (DSMV criteria) during the last 6 months and/or former severe SUD or dependence DSMIV during more than 5 years.
  • Current cognitive remediation programme,
  • Pregnant women, parturients, and lactating women,
  • Individuals deprived of their liberty by a judicial or administrative decision,
  • Individuals of legal age who are the subject of a legal protection measure or unable to express their consent

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Treatment as usual (TAU)Treatment as usual (TAU)-
TAU + cognitive trainingCognitive training-
TAU + cognitive trainingTreatment as usual (TAU)-
TAU + personalized neuroprotective strategiesTreatment as usual (TAU)-
TAU + personalized neuroprotective strategies + cognitive trainingCognitive training-
TAU + personalized neuroprotective strategies + cognitive trainingTreatment as usual (TAU)-
Primary Outcome Measures
NameTimeMethod
Global functioning3 to 4 months after the beginning of intervention

Global functioning will be assessed using the Personal and Social Performance Scale (PSP), a well-validated tool for the measurement of social functioning previously used in early psychosis.

PSP is a 100-point single-item rating scale (minimum value 1; maximum value: 100). The scale evaluates four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviours during a determined reference period

Secondary Outcome Measures
NameTimeMethod
Efficiency of composite personalised care on cognitive functions (Social cognition)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Consensus autour de la COgnition Sociale (CLACOS) (PerSo)

Efficiency of composite personalised care on cognitive functions (Selective attention)3 to 4 Month and 6 to 8 Month after the beginning of intervention

D2-R test

Efficiency of composite personalised care on cognitive functions (Verbal long-term memory)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Hopskins Verbal Learning Test (HVLT) delayed recall

Efficiency of composite personalised care on cognitive functions (Visuospatial learning and memory)3 to 4 Month and 6 to 8 Month after the beginning of intervention

Brief Visuospatial Memory test

Efficiency of composite personalised care on cognitive functions (Planning abilities)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Shopping test (Martin 1972)

Efficiency of composite personalised care on cognitive functions (Speed processing)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Wechsler Adult Intelligence Scale (WAIS) (code)

Efficiency of composite personalised care on cognitive functions (Inhibition control)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Stroop (Incompatibility)

Efficiency of composite personalised care on cognitive functions (Visuospatial long-term memory)3 to 4 Month and 6 to 8 Month after the beginning of intervention

Brief Visuospatial Memory test (BVMT) delayed recall

Efficiency of composite personalised care on cognitive functions (Working Memory)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Wechsler Adult Intelligence Scale (WAIS) (Digit span)

Efficiency of composite personalised care on motivationat baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Behavioral inhibition system (BIS) and behavioral activation system (BAS)

Embodiment ability in virtual reality environmentat baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Embodiment ability in virtual reality environment will be assessed using a simulation of two districts of a lively city via the Vive Pro virtual reality kit

Effect of Composite Personalised Care on Health-related quality-of-life (1)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Short Form -12 items quality of life questionnaire (SF-12) SF-12 is a multipurpose self-report measure of both physical and mental health status

Effect of Composite Personalised Care on Health-related quality-of-life (2)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

European Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L)

EQ-5D-5L investigates 5 dimensions: mobility, self care, usual activities, pain/discomfort, anxiety/depression. These 5 dimensions are rated on 5 levels ranging from no problems to extreme problems.

Effect of Composite Personalised Care on medication adherenceat baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Medication adherence (MARS) is a short assessement (5 items) of the adherence to medication

Acceptability of the program for the e-Health application3 to 4 months after the beginning of intervention

amount of time spent on the application

Level and changes of biological markers (lipid membranes)at baseline and 6 to 8 months after the beginning of intervention

lipid composition of the red blood cells membrane, including the major lipid classes, such as phosphatidylcholine (PC), phosphatidylserine (PS), sphingomyelin (SM), phosphatidylethanolamine (PE), PE plasmalogen and their molecular species)

Longitudinal epigenetic and seric changes associated with outcome (1)at baseline and 6 to 8 months after the beginning of intervention

Levels of RNA (messenger RNA, microRNA, long non-coding RNA) will be assessed using next generation sequencing methods.

Longitudinal epigenetic and seric changes associated with outcome (2)at baseline and 6 to 8 months after the beginning of intervention

Levels of RNA (messenger RNA, microRNA, long non-coding RNA) will be assessed using next generation sequencing methods.

Cost-effectiveness of Composite Personalised Careat the end of the follow-up, up to 4 years

Incremental cost-effectiveness ratios (ICER) will assess the efficiency of CPC vs. TAU (overall and by component). They will be expressed in cost per quality-adjusted life-years (QALY) gained and in cost per PSP point gained.

Budgetary impact analysis of the generalization of Composite Personalised Careat the end of the follow-up, up to 4 years

Total costs and health benefits associated with generalizing CPC will be assessed and compared to TAU over a 5-year period.

Persistence of efficacy on global functioningat baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

Scores at Global Functioning Scale-Social and Role \[120\], measured at V2 and V3. This scale provides a 1 to 10 score separately for social role and for functioning.

Efficiency of Composite Personalised Care (CPC) on clinical outcome (5)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

PANSS (Positive and Negative Syndrome Scale) PANSS is a 30-item scale widely used in schizophrenia research to assess positive and negative psychotic dimensions as well as general symptomatology

Efficiency of Composite Personalised Care (CPC) on clinical outcome (6)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

Clinical Global Impression (CGI) scale. CGI estimates the current severity, of illness on a 7-point scale, as well as evolution and therapeutic index in reference to the clinicians past experiences of similar patients (3 items).

Efficiency of composite personalised care on cognitive functions (Verbal learning and memory)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Hopkins Verbal Learning Test

Efficiency of Composite Personalised Care (CPC) on clinical outcome (1)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

Comprehensive Assessment of At Risk Mental State (CAARMS) CAARMS evaluates seven dimensions of symptomatology. It provides operational criteria to categorise subjects as 'at-risk' or as psychotic (psychosis threshold) on the basis of the first subscale (10 min), 'positive symptoms' encompassing four sub-scales (Unusual Thought Content, Non-Bizarre Ideas, Perceptual Abnormalities, Disorganised Speech)

Efficiency of Composite Personalised Care (CPC) on clinical outcome (3)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

- MADRS (Montgomery-Asberg depression scale). MADRS is a 10 -item scale that evaluates different aspects of depressive symptomatology. It provides a good estimation of the severity of depression and is sensitive to change.

Efficiency of Composite Personalised Care (CPC) on clinical outcome (7)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

Clinical Global Impression (CGI) scale. CGI estimates the current severity, of illness on a 7-point scale, as well as evolution and therapeutic index in reference to the clinicians past experiences of similar patients (3 items).

Efficiency of Composite Personalised Care (CPC) on clinical outcome (2)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

- SOFAS (Social and Occupational Functioning Assessment Scale or EFSP. SOFAS specifically estimates social functioning on a scale between 0 and 100.

Efficiency of composite personalised care on cognitive functions (Flexibility)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

TMT A/B (Reitan, 1959)

Efficiency of Composite Personalised Care (CPC) on clinical outcome (4)at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention

- Brief Psychiatric Rating Scale (BPRS). BPRS is a scale that evaluates general psychiatric symptomatology.

Efficiency of Composite Personalised Care on linguistic and discourse markersat baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

The recording of the interview will allow to extract reliable linguistic metrics that will be processed semi-automatically.

Efficiency of composite personalised care on neurological soft signs (2)at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Electronic Neurological Soft Signs (eNNS) This device incorporates a new, tablet-based and clinically suitable app (behavioral tasks), including tasks designed to probe balance of excitation/inhibition (multi-finger tapping task), body scheme tasks where finger posture recognition is measured and visuomotor sequence learning under variable cognitive load (using visual attentional distractors).

Efficiency of composite personalised care on neurological soft signs (1)at baseline and 6 to 8 months after the beginning of intervention

Neurological Soft Signs rating scale (NSS) assesses five factors: motor coordination, motor integration, sensory integration, quality of lateralization and involuntary movements or posture; as well as extrapyramidal symptoms (Simpson Angus Scale) and lateralization (Edinburgh questionnaire).

Level and changes of biological markers (metabolism of monocarbon compounds)at baseline and 6 to 8 months after the beginning of intervention

dosage of folates, B12 vitamin, homocysteine

Efficiency of composite personalised care on cognitive complaintsat baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention

Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) is a 21-item Likert-type scale that allows a quantitative approach of cognitive complaint.

Patient's satisfaction with the e-health application3 to 4 months after the beginning of intervention

satisfaction score measured by the User Version of the Mobile Application Rating Scale (uMARS)

Trial Locations

Locations (13)

Hôpital La Colombière - CHU Montpellier

🇫🇷

Montpellier, France

CH Orsay

🇫🇷

Orsay, France

CHU Poitiers

🇫🇷

Poitiers, France

Nineteen GHU

🇫🇷

Paris, France

CHU Purpan

🇫🇷

Toulouse, France

C.H. Guillaume Regnier

🇫🇷

Rennes, France

CHRU Brest

🇫🇷

Brest, France

Centre Hospitalier La Chartreuse

🇫🇷

Dijon, France

Hôpital Fontan

🇫🇷

Lille, France

GHU Paris Neurosciences Psychiatrie

🇫🇷

Paris, France

Eldorado - Maison des Adolescents de Meurthe et Moselle

🇫🇷

Nancy, France

Centre Esquirol - CHU CAEN

🇫🇷

Caen, France

CHU Clermont Ferrand

🇫🇷

Clermont-Ferrand, France

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