Study of Bipolar Disorders and Retinal Electrophysiological Markers

Bipolar Disorder Clinical Trial

— BIMAR  

Official title:

Study of Bipolar Disorders and Retinal Electrophysiological Markers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05161546
• Other study ID #: RIPH 2021-03
• Secondary ID: IDRCB 2021-A0164
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2022
• Est. completion date: August 2025

Study information

• Verified date: August 2023
• Source: Centre Psychothérapique de Nancy
• Contact: Grégory GROSS, MD, PhD
• Phone: 03 83 92 67 01
• Email: gregory.gross[@]univ-lorraine.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: August 2025
• Est. primary completion date: July 18, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Device:
• 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.
• 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.

Behavioral:
• 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.

Device:
• 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.

Locations

Country	Name	City	State
France	Centre Psychothérapique de Nancy	Laxou	Nancy

Sponsors (2)

Lead Sponsor	Collaborator
Centre Psychothérapique de Nancy	BioSerenity

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mini International Neuropsychiatric Interview (MINI)	questionnaire to diagnose psychiatric disorders	Day 0 (=day of inclusion)
Other	Montgomery-Asberg Depression Rating Scale (MADRS)	rating scale measuring depressive symptoms	Day 0 (=day of inclusion)
Other	Montgomery-Asberg Depression Rating Scale (MADRS)	rating scale measuring depressive symptoms	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Young Mania Rating Scale (YMRS)	rating scale measuring manic symptoms	Day 0 (=day of inclusion)
Other	Young Mania Rating Scale (YMRS)	rating scale measuring manic symptoms	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Pittsburgh Sleep Quality Index (PSQI)	assess the subjective quality of sleep during the past month	Day 0 (=day of inclusion)
Other	Pittsburgh Sleep Quality Index (PSQI)	assess the subjective quality of sleep during the past month	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Insomnia Severity Index (ISI)	assess the severity of insomnia	Day 0 (=day of inclusion)
Other	Insomnia Severity Index (ISI)	assess the severity of insomnia	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Epworth sleepiness scale (ESS)	assess the daytime sleepiness	Day 0 (=day of inclusion)
Other	Epworth sleepiness scale (ESS)	assess the daytime sleepiness	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Horne and Ostberg circadian typology questionnaire	assess the circadian rhythm type by evaluating the daily sleep-wake habits and the times of day when certain activities are performed with preferences	Day 0 (=day of inclusion)
Other	Horne and Ostberg circadian typology questionnaire	assess the circadian rhythm type by evaluating the daily sleep-wake habits and the times of day when certain activities are performed with preferences	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Composite Scale of Morningness (CSM)	measure of behavioral temporal preference	Day 0 (=day of inclusion)
Other	Composite Scale of Morningness (CSM)	measure of behavioral temporal preference	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Circadian Type Inventory (CTI)	assess of amplitude and stability of rhythms	Day 0 (=day of inclusion)
Other	Circadian Type Inventory (CTI)	assess of amplitude and stability of rhythms	at the visit n ° 2 (=between Day 22 and Day 27)
Other	The Berlin Questionnaire	estimate the risk of Obstructive Sleep Apnea syndrome	Day 0 (=day of inclusion)
Other	The Berlin Questionnaire	estimate the risk of Obstructive Sleep Apnea syndrome	at the visit n ° 2 (=between Day 22 and Day 27)
Other	Quick Inventory of Depressive Symptomatology self-report (QIDS-SR)	self reported rating scale measuring depressive symptoms	Day 0 (=day of inclusion)
Other	Altman Self-Rating Mania Scale (ALTMAN)	self reported rating scale measuring manic symptoms	Day 0 (=day of inclusion)
Other	State Trait Inventory Anxiety (STAI-A)	self reported rating scale measuring anxiety symptoms	Day 0 (=day of inclusion)
Other	Multidimensional Assessment of Thymic States (MATHYS)	self reported assessment of emotional reactivity	Day 0 (=day of inclusion)
Other	Patient Rated Inventory of Side Effects (PRISE-M)	self reported assessment of tolerance to treatments	Day 0 (=day of inclusion)
Other	Medication Adherence Rating (MARS)	self reported assessment of adherence to treatments	Day 0 (=day of inclusion)
Other	Alda Scale	assess response to lithium treatment	Day 0 (=day of inclusion)
Other	Functioning Assessment Short Test (FAST)	assess patient's functioning	Day 0 (=day of inclusion)
Other	Clinical Global Impression Scale (CGI)	assess patient's functioning	Day 0 (=day of inclusion)
Other	Affective Instability Measure (AIM)	assess oscillations of intense affect	Day 0 (=day of inclusion)
Other	Affective Lability Scale (ALS)	assess the emotional lability	Day 0 (=day of inclusion)
Other	Buss-Durkee Hostility Inventory (BDHI)	assess the hostility	Day 0 (=day of inclusion)
Other	Barrat Impulsivity Scale (BIS-10)	assess the impulsivity	Day 0 (=day of inclusion)
Other	Wender Utah Rating Scale (WURS)	check for a history of attention deficit hyperactivity disorder	Day 0 (=day of inclusion)
Other	Childhood Trauma Questionnaire (CTQ)	check for trauma in childhood	Day 0 (=day of inclusion)
Other	Fagerström test	assess the tobacco addiction	Day 0 (=day of inclusion)
Other	Edinburgh Handedness Inventory	assess the manual preference	Day 0 (=day of inclusion)
Other	Spectral Domain Optical Coherence Tomography (SD-OCT)	evaluation of retinal structure	between Day 23 and Day 28
Other	Optical Coherence Tomography Angiography (OCT-A)	evaluation of retinal vascularity	between Day 23 and Day 28
Primary	Modification of amplitude measured with flash and pattern electroretinogram	amplitude in microvolt	Day 0 (=day of inclusion)
Primary	Modification of implicite time measured with flash and pattern electroretinogram	implicite time in millisecond	Day 0 (=day of inclusion)
Secondary	Modification of amplitude measured with electroencephalogram	amplitude of the P100, N170 and N200 waves amplitude in microvolt	Day 0 (=day of inclusion)
Secondary	Modification of latency measured with electroencephalogram	latency of the P100, N170 and N200 waves latency in millisecond	Day 0 (=day of inclusion)
Secondary	Actigraphy	evaluation of sleep/wake cycles	from Day1 to Day21
Secondary	Sleep diary	self reported tool of sleeping and waking times	from Day 1 to Day 21
Secondary	Visual Object and Space Perception battery (VOSP)	test of visual cognition	visit n ° 2 (=between Day 22 and Day 27)
Secondary	California Verbal Learning Test (CVLT)	assessment of verbal episodic memory	visit n ° 2 (=between Day 22 and Day 27)
Secondary	Continuous Performance Task (CPT-III)	test of sustained attention	visit n ° 2 (=between Day22 and Day27)
Secondary	Verbal Fluency Task	test of verbal functioning	visit n ° 2 (=between Day 22 and Day 27)
Secondary	Test of Attention Assessment (TAP)	test of attentional performance	visit n ° 2 (=between Day 22 and Day 27)
Secondary	Montreal Cognitive Assessment (MoCA)	screening assessment for detecting cognitive impairment	visit n ° 2 (=between Day 22 and Day 27)