Study of Bipolar Disorders and Retinal Electrophysiological Markers

NCT ID: NCT05161546

Last Updated: 2024-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-18

Study Completion Date

2023-08-08

Brief Summary

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The BIMAR study aims to compare electrophysiological data measured with electroretinogram (ERG) and electroencephalogram (EEG) between a group of euthymic patients with bipolar disorder (BD) and a group of healthy controls subjects.

Secondarily, the investigators also want to:

* Compare combined electrophysiological measurements with ERG and EEG between the two groups.
* Identify relations between clinical, neuropsychological and circadian phenotypes in patients with BD and electrophysiological measurements measured with ERG and EEG.

The main hypothesis of the investigators is that differences exist in the ERG and EEG measurements between subjects with BD and healthy subjects. Those differences could be identified as candidate markers for BD which, if confirmed in later studies, could be used in current practice to guide the management of patients with BD.

Detailed Description

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Bipolar disorders (BD) is a common, chronic and disabling psychiatric condition. In addition to being characterized by significant clinical heterogeneity, notable disturbances of sleep and cognitive function are frequently observed in all phases of the disease. Currently, there is no readily available biomarker in current clinical practice to help diagnose or predict the disease course. Thus, identification of biomarkers in BD is today a major challenge. In this context, the study of electrophysiological biomarkers based on electroretinogram (ERG) and electroencephalogram (EEG) measurements in BD seems highly promising. The BiMAR study aims to compare electrophysiological data measured with ERG and EEG between a group of euthymic patients with BD and a group of healthy control subjects. Secondarily, the investigators will also describe the existing potential relationship between clinical, sleep and neuropsychological phenotypes of patients and electrophysiological data.

The BiMAR study is a comparative and monocentric study carried out at the Expert Center for BD in Nancy, France. In total, 70 euthymic adult patients with BD and 70 healthy control subjects will be recruited. Electrophysiological recordings with ERG and EEG will be performed with a virtual reality headset after a standardized clinical evaluation to all participants. Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit. The primary outcome will be electrophysiological measurements with ERG flash and pattern. Secondary outcomes will be EEG data, sleep settings, clinical and neuropsychological assessments. For patients only, a complementary ancillary study, carried out at the University Hospital of Nancy, will be proposed to assess the retinal structure and microvascularization using Optical Coherence Tomography. Recruitment will begin in December 2021 and will continue until the end of June 2023.

The BiMAR study will contribute to identifying candidate ERG electrophysiological markers for helping the diagnosis of BD and identify subgroups of patients with different clinical profiles. Eventually, this would allow earlier diagnosis and personalized therapeutic interventions.

Conditions

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Bipolar Disorder

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

The BiMAR study is an open-label and non-randomized comparative monocentric study applied in psychiatry and neuroscience.

This research included two groups of adult subjects: a group of patients with BD in the euthymic phase and a group of healthy control subjects.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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patients with bipolar disorder (BD)

Electrophysiological recordings with ERG and EEG will be performed with a virtual reality headset after a standardized clinical evaluation (first visit).

Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit.

Between day 23 and day 28 (after the second visit), patients will be offered to assess the retinal structure and microvascularization using Spectral Domain Optical Coherence Tomography (SD-OCT) and OCT-Angiography (OCT-A).

Group Type EXPERIMENTAL

EEG and ERG measurements (Retinaute®, BioSerenity)

Intervention Type DEVICE

The Retinaute® is a portable medical device developed by BioSerenity, France, for performing flash and pattern ERG. It comes in the form of a virtual reality headset, which can be used in outpatient facilities. It is non-invasive and uses skin electrodes for the collection of parameters.

ERG signals will be supplemented with 4 EEG channels, via cup electrodes applied to the skull and allowing the concomitant performance of an EEG.

Actigraphy (Motion Watch 8®, CamNtech)

Intervention Type DEVICE

Actigraphy is an ecological and non-invasive method allowing a reliable characterization of the sleep/wake cycle. It is a portable system for continuously measuring the motor activity of an individual and appreciating the alternation of activity periods (wakefulness) and rest periods (sleep).

An actigraph (MotionWatch8®, CamNtech) looks like a wristwatch that will be worn continuously, by convention on the wrist of the non-dominant hand, over periods ranging from several days to several weeks (here 21 days). Actigraphy does not present a known risk.

Neuropsychological assessments

Intervention Type BEHAVIORAL

The purpose of this assessment is to establish a cognitive profile for each participant. It uses a series of tests widely described in the literature and commonly used today.

Optical Coherence Tomography (OCT)

Intervention Type DEVICE

The Spectral Domain Optical Coherence Tomography (SD-OCT) is a modern ocular imaging process using infrared radiation and allowing to obtain in a few seconds, and in a non-invasive way, images in section of the eye. The OCT-Angiography (OCT-A) module increments on the OCT. It can detect the movement of the blood elements from sequential SD-OCT slices taken at the same location of the retina and obtain a map of the retinal and choroidal vessels, without injection of fluorescent dye. The device used for both exams will be the OCT spectral RS 3000 Advance 2 + Angioscan (NIDEK, Gamagori, Japan). SD-OCT and OCT-A examinations are fast, painless, non-contact and last less than a minute. There is no particular risk.

healthy volunteers

Electrophysiological recordings with ERG and EEG will be performed with a virtual reality headset after a standardized clinical evaluation (first visit).

Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit.

Group Type ACTIVE_COMPARATOR

EEG and ERG measurements (Retinaute®, BioSerenity)

Intervention Type DEVICE

The Retinaute® is a portable medical device developed by BioSerenity, France, for performing flash and pattern ERG. It comes in the form of a virtual reality headset, which can be used in outpatient facilities. It is non-invasive and uses skin electrodes for the collection of parameters.

ERG signals will be supplemented with 4 EEG channels, via cup electrodes applied to the skull and allowing the concomitant performance of an EEG.

Actigraphy (Motion Watch 8®, CamNtech)

Intervention Type DEVICE

Actigraphy is an ecological and non-invasive method allowing a reliable characterization of the sleep/wake cycle. It is a portable system for continuously measuring the motor activity of an individual and appreciating the alternation of activity periods (wakefulness) and rest periods (sleep).

An actigraph (MotionWatch8®, CamNtech) looks like a wristwatch that will be worn continuously, by convention on the wrist of the non-dominant hand, over periods ranging from several days to several weeks (here 21 days). Actigraphy does not present a known risk.

Neuropsychological assessments

Intervention Type BEHAVIORAL

The purpose of this assessment is to establish a cognitive profile for each participant. It uses a series of tests widely described in the literature and commonly used today.

Interventions

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EEG and ERG measurements (Retinaute®, BioSerenity)

The Retinaute® is a portable medical device developed by BioSerenity, France, for performing flash and pattern ERG. It comes in the form of a virtual reality headset, which can be used in outpatient facilities. It is non-invasive and uses skin electrodes for the collection of parameters.

ERG signals will be supplemented with 4 EEG channels, via cup electrodes applied to the skull and allowing the concomitant performance of an EEG.

Intervention Type DEVICE

Actigraphy (Motion Watch 8®, CamNtech)

Actigraphy is an ecological and non-invasive method allowing a reliable characterization of the sleep/wake cycle. It is a portable system for continuously measuring the motor activity of an individual and appreciating the alternation of activity periods (wakefulness) and rest periods (sleep).

An actigraph (MotionWatch8®, CamNtech) looks like a wristwatch that will be worn continuously, by convention on the wrist of the non-dominant hand, over periods ranging from several days to several weeks (here 21 days). Actigraphy does not present a known risk.

Intervention Type DEVICE

Neuropsychological assessments

The purpose of this assessment is to establish a cognitive profile for each participant. It uses a series of tests widely described in the literature and commonly used today.

Intervention Type BEHAVIORAL

Optical Coherence Tomography (OCT)

The Spectral Domain Optical Coherence Tomography (SD-OCT) is a modern ocular imaging process using infrared radiation and allowing to obtain in a few seconds, and in a non-invasive way, images in section of the eye. The OCT-Angiography (OCT-A) module increments on the OCT. It can detect the movement of the blood elements from sequential SD-OCT slices taken at the same location of the retina and obtain a map of the retinal and choroidal vessels, without injection of fluorescent dye. The device used for both exams will be the OCT spectral RS 3000 Advance 2 + Angioscan (NIDEK, Gamagori, Japan). SD-OCT and OCT-A examinations are fast, painless, non-contact and last less than a minute. There is no particular risk.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Patients:

* been diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) diagnostic criteria using the Mini International Neuropsychiatric Interview (MINI)
* currently euthymic for at least 3 months prior to the study, as defined by a score below 10 on the Montgomery-Asberg Depression Rating Scale (MADRS) which assesses depression and by a score below 8 on the Young Mania Rating Scale (YMRS) which assesses mania
* age 18 or more
2. Healthy volunteers:

* not suffer from a personal psychiatric pathology verified with the MINI
* age 18 or more

Exclusion Criteria

* suffer from psychiatric pathology or substance use disorders according to DSM-IV criteria measured with the MINI, excluding BD for the patient group
* suffer from neurological or retinal pathology
* having a shift work or a get-lag in the last 15 days
* criteria incompatible with the use of the virtual reality headset (Retinaute®,BioSerenity) like having an allergy to one of the components of the textile
* persons treated by sismotherapy during the past year
* persons with an uncorrected visual impairment or disabling hearing impairment that does not allow neuropsychological tests to be performed
* subjects with an intellectual disability making it difficult to participate in the study or to understand and follow informations provided to them
* adults legally protected
* pregnant or breastfeeding women
* subjects already participating in another interventional trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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BioSerenity

INDUSTRY

Sponsor Role collaborator

Centre Psychothérapique de Nancy

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas SCHWITZER, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Psychothérapique de Nancy

Locations

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Centre Psychothérapique de Nancy

Laxou, Nancy, France

Site Status

Countries

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France

References

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Schwitzer T, Schwan R, Bubl E, Lalanne L, Angioi-Duprez K, Laprevote V. Looking into the brain through the retinal ganglion cells in psychiatric disorders: A review of evidences. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jun 2;76:155-162. doi: 10.1016/j.pnpbp.2017.03.008. Epub 2017 Mar 20.

Reference Type BACKGROUND
PMID: 28336492 (View on PubMed)

Tan A, Schwitzer T, Conart JB, Angioi-Duprez K. Study of retinal structure and function in patients with major depressive disorder, bipolar disorder or schizophrenia: A review of the literature. J Fr Ophtalmol. 2020 May;43(5):e157-e166. doi: 10.1016/j.jfo.2020.04.004. Epub 2020 May 4.

Reference Type BACKGROUND
PMID: 32381369 (View on PubMed)

Hebert M, Merette C, Gagne AM, Paccalet T, Moreau I, Lavoie J, Maziade M. The Electroretinogram May Differentiate Schizophrenia From Bipolar Disorder. Biol Psychiatry. 2020 Feb 1;87(3):263-270. doi: 10.1016/j.biopsych.2019.06.014. Epub 2019 Jun 27.

Reference Type BACKGROUND
PMID: 31443935 (View on PubMed)

Gross G, Tursini K, Albuisson E, Angioi-Duprez K, Conart JB, Louis Dorr V, Schwan R, Schwitzer T. Bipolar disorders and retinal electrophysiological markers (BiMAR): Study protocol for a comparison of electroretinogram measurements between subjects with bipolar disorder and a healthy control group. Front Psychiatry. 2022 Sep 8;13:960512. doi: 10.3389/fpsyt.2022.960512. eCollection 2022.

Reference Type DERIVED
PMID: 36159928 (View on PubMed)

Other Identifiers

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IDRCB 2021-A01644-37

Identifier Type: OTHER

Identifier Source: secondary_id

RIPH 2021-03

Identifier Type: -

Identifier Source: org_study_id

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