Clinical trial NCT05796401: Efficiency of a Composite Personalised Care on Functional Outcome in Early Psychosis
Official title: PsyCARE Trial - "Efficiency of a Composite Personalised Care on Functional Outcome in Early Psychosis : A Prospective Randomised Controlled Trial "
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Psychosis
Lead sponsor: Centre Hospitalier St Anne
Sponsor class: OTHER
First posted: 2023-04-03
Enrollment: 500
Sex: ALL
Minimum age (years): 15
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Phase III, Prospective Randomised Open, Blinded End-point (PROBE) controlled trial stratified according to the developmental burden and centre, with 2x2 factorial designs (equivalent to a 4-arms clinical trial) in a 1:1:1:1 ratio.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Global functioning
timeFrame: 3 to 4 months after the beginning of intervention
Secondary outcomes:
measure: Persistence of efficacy on global functioning
timeFrame: 6 to 8 months after the beginning of intervention
measure: Persistence of efficacy on global functioning
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (1)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (2)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (3)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (4)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (5)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (6)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care (CPC) on clinical outcome (7)
timeFrame: at baseline, then 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of Composite Personalised Care on linguistic and discourse markers
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on neurological soft signs (1)
timeFrame: at baseline and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on neurological soft signs (2)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive complaints
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Verbal learning and memory)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Flexibility)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Social cognition)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Selective attention)
timeFrame: 3 to 4 Month and 6 to 8 Month after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Verbal long-term memory)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Visuospatial learning and memory)
timeFrame: 3 to 4 Month and 6 to 8 Month after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Planning abilities)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Speed processing)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Inhibition control)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Visuospatial long-term memory)
timeFrame: 3 to 4 Month and 6 to 8 Month after the beginning of intervention
measure: Efficiency of composite personalised care on cognitive functions (Working Memory)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Efficiency of composite personalised care on motivation
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Embodiment ability in virtual reality environment
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Effect of Composite Personalised Care on Health-related quality-of-life (1)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Effect of Composite Personalised Care on Health-related quality-of-life (2)
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Effect of Composite Personalised Care on medication adherence
timeFrame: at baseline, 3 to 4 months and 6 to 8 months after the beginning of intervention
measure: Acceptability of the program for the e-Health application
timeFrame: 3 to 4 months after the beginning of intervention
measure: Patient's satisfaction with the e-health application
timeFrame: 3 to 4 months after the beginning of intervention
measure: Level and changes of biological markers (metabolism of monocarbon compounds)
timeFrame: at baseline and 6 to 8 months after the beginning of intervention
measure: Level and changes of biological markers (lipid membranes)
timeFrame: at baseline and 6 to 8 months after the beginning of intervention
measure: Longitudinal epigenetic and seric changes associated with outcome (1)
timeFrame: at baseline and 6 to 8 months after the beginning of intervention
measure: Longitudinal epigenetic and seric changes associated with outcome (2)
timeFrame: at baseline and 6 to 8 months after the beginning of intervention
measure: Cost-effectiveness of Composite Personalised Care
timeFrame: at the end of the follow-up, up to 4 years
measure: Budgetary impact analysis of the generalization of Composite Personalised Care
timeFrame: at the end of the follow-up, up to 4 years
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU Brest
city: Caen
country: France
facility: Centre Esquirol - CHU CAEN
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Dijon
country: France
facility: Centre Hospitalier La Chartreuse
city: Lille
country: France
facility: Hôpital Fontan
city: Montpellier
country: France
facility: Hôpital La Colombière - CHU Montpellier
city: Nancy
country: France
facility: Eldorado - Maison des Adolescents de Meurthe et Moselle
city: Orsay
country: France
facility: CH Orsay
city: Paris
country: France
facility: GHU Paris Neurosciences Psychiatrie
city: Paris
country: France
facility: Nineteen GHU
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: C.H. Guillaume Regnier
city: Toulouse
country: France
facility: CHU Purpan
Study officials:
References: