Clinical trial NCT05161546: Study of Bipolar Disorders and Retinal Electrophysiological Markers
Official title: Study of Bipolar Disorders and Retinal Electrophysiological Markers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Bipolar Disorder
Keywords: bipolar disorder
biomarker
electroretinogram
electroencephalogram
neurocognition
actigraphy
retina
Lead sponsor: Centre Psychothérapique de Nancy
Sponsor class: OTHER
Collaborators: name: BioSerenity
First posted: 2021-12-17
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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 for all participants (patients and healthy volunteers):

* 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

Primary outcomes:
measure: Modification of amplitude measured with flash and pattern electroretinogram
timeFrame: Day 0 (=day of inclusion)
measure: Modification of implicite time measured with flash and pattern electroretinogram
timeFrame: Day 0 (=day of inclusion)
Secondary outcomes:
measure: Modification of amplitude measured with electroencephalogram
timeFrame: Day 0 (=day of inclusion)
measure: Modification of latency measured with electroencephalogram
timeFrame: Day 0 (=day of inclusion)
measure: Actigraphy
timeFrame: from Day1 to Day21
measure: Sleep diary
timeFrame: from Day 1 to Day 21
measure: Visual Object and Space Perception battery (VOSP)
timeFrame: visit n ° 2 (=between Day 22 and Day 27)
measure: California Verbal Learning Test (CVLT)
timeFrame: visit n ° 2 (=between Day 22 and Day 27)
measure: Continuous Performance Task (CPT-III)
timeFrame: visit n ° 2 (=between Day22 and Day27)
measure: Verbal Fluency Task
timeFrame: visit n ° 2 (=between Day 22 and Day 27)
measure: Test of Attention Assessment (TAP)
timeFrame: visit n ° 2 (=between Day 22 and Day 27)
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: visit n ° 2 (=between Day 22 and Day 27)
Other outcomes:
measure: Mini International Neuropsychiatric Interview (MINI)
timeFrame: Day 0 (=day of inclusion)
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Day 0 (=day of inclusion)
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Young Mania Rating Scale (YMRS)
timeFrame: Day 0 (=day of inclusion)
measure: Young Mania Rating Scale (YMRS)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Day 0 (=day of inclusion)
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Insomnia Severity Index (ISI)
timeFrame: Day 0 (=day of inclusion)
measure: Insomnia Severity Index (ISI)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Epworth sleepiness scale (ESS)
timeFrame: Day 0 (=day of inclusion)
measure: Epworth sleepiness scale (ESS)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Horne and Ostberg circadian typology questionnaire
timeFrame: Day 0 (=day of inclusion)
measure: Horne and Ostberg circadian typology questionnaire
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Composite Scale of Morningness (CSM)
timeFrame: Day 0 (=day of inclusion)
measure: Composite Scale of Morningness (CSM)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Circadian Type Inventory (CTI)
timeFrame: Day 0 (=day of inclusion)
measure: Circadian Type Inventory (CTI)
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: The Berlin Questionnaire
timeFrame: Day 0 (=day of inclusion)
measure: The Berlin Questionnaire
timeFrame: at the visit n ° 2 (=between Day 22 and Day 27)
measure: Quick Inventory of Depressive Symptomatology self-report (QIDS-SR)
timeFrame: Day 0 (=day of inclusion)
measure: Altman Self-Rating Mania Scale (ALTMAN)
timeFrame: Day 0 (=day of inclusion)
measure: State Trait Inventory Anxiety (STAI-A)
timeFrame: Day 0 (=day of inclusion)
measure: Multidimensional Assessment of Thymic States (MATHYS)
timeFrame: Day 0 (=day of inclusion)
measure: Patient Rated Inventory of Side Effects (PRISE-M)
timeFrame: Day 0 (=day of inclusion)
measure: Medication Adherence Rating (MARS)
timeFrame: Day 0 (=day of inclusion)
measure: Alda Scale
timeFrame: Day 0 (=day of inclusion)
measure: Functioning Assessment Short Test (FAST)
timeFrame: Day 0 (=day of inclusion)
measure: Clinical Global Impression Scale (CGI)
timeFrame: Day 0 (=day of inclusion)
measure: Affective Instability Measure (AIM)
timeFrame: Day 0 (=day of inclusion)
measure: Affective Lability Scale (ALS)
timeFrame: Day 0 (=day of inclusion)
measure: Buss-Durkee Hostility Inventory (BDHI)
timeFrame: Day 0 (=day of inclusion)
measure: Barrat Impulsivity Scale (BIS-10)
timeFrame: Day 0 (=day of inclusion)
measure: Wender Utah Rating Scale (WURS)
timeFrame: Day 0 (=day of inclusion)
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: Day 0 (=day of inclusion)
measure: Fagerström test
timeFrame: Day 0 (=day of inclusion)
measure: Edinburgh Handedness Inventory
timeFrame: Day 0 (=day of inclusion)
measure: Spectral Domain Optical Coherence Tomography (SD-OCT)
timeFrame: between Day 23 and Day 28
measure: Optical Coherence Tomography Angiography (OCT-A)
timeFrame: between Day 23 and Day 28
Locations:
city: Laxou
country: France
facility: Centre Psychothérapique de Nancy
state: Nancy
Study officials:
affiliation: Centre Psychothérapique de Nancy
name: Thomas SCHWITZER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.