REtinal and VIsual Cortical Response in Early PSYchosis

Healthy Controls Clinical Trial

— REVIPSY  

Official title:

REtinal and VIsual Cortical Response in Early PSYchosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05167396
• Other study ID #: RIPH 2021-04
• Secondary ID: n° IDRCB 2021-A0
• Status: Recruiting
• Phase: N/A
• Start date: January 26, 2022
• Est. completion date: January 26, 2026

Study information

• Verified date: August 2023
• Source: Centre Psychothérapique de Nancy
• Contact: Irving REMY
• Phone: 0383925267
• Email: irving.remy[@]bioserenity.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the REVIPSY study is to measure retinal and the visual cortical electrophysiological responses in situations at risk of psychosis in patients who have experienced a first psychotic episode. A perspective of this project will be to create new electrophysiological biomarkers predictive of the risk of conversion to psychosis

Description:

The severity of psychotic disorders and their disabling potential in young patients represent a major public health problem. These populations are affected by high-level cognitive disorders associated with highly integrative functions. However, there is increasing evidence of lower-level impairments, including vision. Indeed, the literature reports electrophysiological abnormalities at the retinal level, reflected by an alteration of the signal transmission in the retinal ganglion cells (RGC), photoreceptors and bipolar cells. At the cortical level, numerous studies report electrophysiological abnormalities associated with the activity of the primary visual areas. These both electrophysiological measurements have the advantage of being objective, reliable and reproducible, thus leading to new research perspectives concerning the link between retinal and cortical measures in psychosis. These measures could also be interesting for the detection of the risk of conversion to psychosis, before it develops.

The transition to a state of psychosis is in fact marked by the appearance of symptoms, which can occur several years before the diagnosis and impact the duration of the untreated psychosis. Thus, the notion of a clinical state at high risk of psychosis (CHRP) defines a population of patients said to be at risk of psychosis. These symptoms precede the occurrence of the first psychotic episode (FEP), indicating the clear transition to psychotic illness. The questions that arise at the present time concerned the early detection and intervention of psychosis during this prodromal phase. This detection could be done via electrophysiological measures associated to the visual processing, but also via measures of neuropsychological evaluations and behavioral measures.

That is why, a study on retinal and visual cortical alterations coupled with neuropsychological assessments and behavioral measures in populations at risk of populations at risk of CHRP psychosis and in FEP would potentially reveal predictive biomarkers of the pathology. Such a project could lead to the development of retino-cortical biomarkers in mental health and will eventually lead to to create ultra-portable, reliable and routinely usable measurement devices for the early detection of psychosis in clinic.

Main objective: To measure retinal and visual cortical electrophysiological responses in clinical subjects at high risk of psychosis (CHRP) in comparison with first-episode psychotic patients (FEP) and healthy controls (CS)

Secondary objective(s) :

Compare ERG traces obtained from the "Retinaute" portable ERG device produced by the company BioSerenity with ERG traces obtained from a standard device ERG measurement device "MyPackOne" produced by the company Metrovision among healthy controls

To measure performance on neuropsychological tests in clinical subjects at high risk of psychosis (CHRP) compared to patients with a first episode of psychosis (FEP)

Measuring temporal prediction in tactile modality (unimodal) with a motor task, in clinical subjects at high risk of psychosis (CHRP) in comparison with first-episode patients (FEP) and healthy controls (CS)

Measuring temporal prediction in visual and tactile (multimodal) modalities/Measuring temporal prediction in visual modality (unimodal) with a classical perceptual task in clinical subjects at high risk of psychosis (CHRP) in comparison with patients with a first psychotic episode with a first episode of psychosis (FEP) and healthy controls (CS)

To compare the sensitivity of behavioural and EEG measures to the prediction of tactile vs. visual stimuli, and multimodal vs. unimodal

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 26, 2026
• Est. primary completion date: January 26, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

1. Inclusion Criteria:

1. All groups

Age and gender matching

Age between 18 and 40

Enrolled in a social security plan

Normal or corrected-to-normal visual acuity verified by Monoyer test

In women of childbearing age: negative urine pregnancy test at the inclusion visit

Person who has received and understood prior information about the study

Person who has given free and informed written consent prior to any participation in the study

2. Healthy control group (HC; n=30)

Met "all groups" criteria

No current disorders as assessed by the MINI global assessment

No lifetime (hypo)manic episodes or psychotic disorders and current

No current or past disorders by CAARMS assessment

No current disorders according to ICD-10 criteria

No positive family history (parents/first degree) for affective affective, non-affective psychoses or major affective disorders

No regular use (more than 3 psychotropic medications: benzodiazepines, hypnotics,antidepressants, antipsychotics or mood regulators or psychostimulants) during the past last 12 months

3. High clinical risk group for psychosis (CHRP; n=30)

Met "all groups" criteria, Assessment at CAARMS:

• Attenuated positive symptoms (APS)

• OR Brief Intermittent Psychotic Symptoms (BIPS)

• OR Attenuated psychosis of sub-laminar frequency

• OR sub-laminar attenuated psychosis

Antipsychotic treatment with a cumulative dose of equivalent chlorpromazine <2500mg lifetime (1)

4. First Episode Psychosis (FEP; n=30)

All-group criteria met CAARMS assessment: Psychosis/antipsychotic treatment threshold treatment threshold achieved at CAARMS

Antipsychotic treatment with a cumulative dose of equivalent chlorpromazine <2500mg lifetime (1)

2. Exclusion Criteria (all groups):

Impairment of the subject that makes it difficult or impossible to participate in the or comprehension of the information provided to him/her

Dyslexia

Substance use disorder according to CIM-10

Neurological history including progressive neurological pathology

Progressive retinal disease

Chronic glaucoma

Ophthalmologic pathology affecting visual acuity

Current ocular infection

Major under guardianship, curatorship or safeguard of justice

Pregnant or breastfeeding women

Persons in a life-threatening emergency situation

Result of the preliminary medical examination incompatible with the research

Patient presenting a suicidal risk.

Criteria incompatible with the use of the Retinaute:

• Allergy to silver

• Known or suspected allergy to any of the following components:

polyamide, polyester, elastane, latex, rubber, silicone, or any synthetic material as well as to cotton in case the device is used without the device is used without a protective head covering

• Sensory disorders making the patient insensitive to pain on the skin.

• Behavioral problems making the patient extremely agitation or aggression.

• Mental disorders incompatible with the use of the device.

• Seizure disorder.

• Open wound in an area covered or wrapped by the device.

• User at high risk of contagion.

• Wearing an implantable medical device (e.g. pacemaker)

• Pregnant women, women in labor or nursing mothers.

• Allergy or skin sensitivity to one of the components of the cream Elefix or equivalent on the market: coconut oil, egg oil, propylene glycol egg oil, propylene glycol, glycerin, lanolin...

• Allergy or skin sensitivity to one of the components of the cream NuPrep or market equivalent

Participation in another interventional study (exclusion period included)

Related Conditions & MeSH terms

• Healthy Controls
• Mental Disorders
• Prodromal Schizophrenia
• Prodromal Symptoms
• Psychotic Disorders
• Psychotic Episode
• Schizophrenia

Intervention

Device:
• Retinaute (BioSerenity)
Wearable device in the form of a virtual reality headset for the recording of electrophysiological measurements such as electroretinogram (ERG) and electrocenphalogram (EEG), ISCEV standards
• EEG Headset 64 electrodes (BioSemi)
EEG headset with 64 electrodes for the recording of visual cortical electrophysiological signals
• MonPackOne (Metrovision)
Standard device for the recording of electroretinography (ERG) measurements, ISCEV standards WARNING : Device used only in 3 healthy controls to address the secondary objective

Locations

Country	Name	City	State
France	Centre Psychothérapeutique de Nancy	Laxou

Sponsors (3)

Lead Sponsor	Collaborator
Centre Psychothérapique de Nancy	BioSerenity, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (7)

Butler PD, Martinez A, Foxe JJ, Kim D, Zemon V, Silipo G, Mahoney J, Shpaner M, Jalbrzikowski M, Javitt DC. Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. Brain. 2007 Feb;130(Pt 2):417-30. doi: 10.1093/brain/awl233. Epub 2006 Sep 19. — View Citation

Demmin DL, Davis Q, Roche M, Silverstein SM. Electroretinographic anomalies in schizophrenia. J Abnorm Psychol. 2018 May;127(4):417-428. doi: 10.1037/abn0000347. — View Citation

Kim DW, Shim M, Song MJ, Im CH, Lee SH. Early visual processing deficits in patients with schizophrenia during spatial frequency-dependent facial affect processing. Schizophr Res. 2015 Feb;161(2-3):314-21. doi: 10.1016/j.schres.2014.12.020. Epub 2014 Dec 29. — View Citation

Knebel JF, Javitt DC, Murray MM. Impaired early visual response modulations to spatial information in chronic schizophrenia. Psychiatry Res. 2011 Sep 30;193(3):168-76. doi: 10.1016/j.pscychresns.2011.02.006. Epub 2011 Jul 20. — View Citation

Laprevote V, Heitz U, Di Patrizio P, Studerus E, Ligier F, Schwitzer T, Schwan R, Riecher-Rossler A. [Why and how to treat psychosis earlier?]. Presse Med. 2016 Nov;45(11):992-1000. doi: 10.1016/j.lpm.2016.07.011. Epub 2016 Aug 21. French. — View Citation

Moghimi P, Torres Jimenez N, McLoon LK, Netoff TI, Lee MS, MacDonald A 3rd, Miller RF. Electoretinographic evidence of retinal ganglion cell-dependent function in schizophrenia. Schizophr Res. 2020 May;219:34-46. doi: 10.1016/j.schres.2019.09.005. Epub 2019 Oct 12. — View Citation

Tan A, Schwitzer T, Conart JB, Angioi-Duprez K. [Retinal investigations in patients with major depressive disorder, bipolar disorder or schizophrenia: A review of the literature]. J Fr Ophtalmol. 2020 Sep;43(7):586-597. doi: 10.1016/j.jfo.2019.10.029. Epub 2020 Jul 4. French. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	N95 wave	Amplitude	Day1
Primary	a wave	Amplitude	Day1
Primary	b wave	Amplitude	Day1
Primary	P100 wave	Amplitude	Day1
Secondary	Visual Object and Space Perception (VOSP)	Score	Day1
Secondary	Verbal Fluency	Score	Day1
Secondary	Working Memory	Score	Day1
Secondary	Betarythm (EEG oscillatory responses)	Amplitude	Day1
Secondary	Contingent Negative Variation (CNV)	Amplitude reaction time between a warning and a go signal as measured by electroencephalography (EEG)	Day1
Secondary	CPT-AX (Continuous Performance Task version AX)	Score	Day1
Secondary	fNART (French adaptation of National Adult Reading Test)	Score	Day1
Secondary	TAP (Test of Attentional Performance)	Score	Day1