University Hospital, Grenoble — Biomedical Watch V2

Traitements6programmes

Essais3liés

Publications6liées

SourceDBlocale

Traitements

6

Molécule	Indication / population	Phase	Objectif	Pays	Résultat
Anti-ficolin-3 Autoantibodies in Lupus NephritisSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, clinical data were obtained from medical files and blood samples were selected from preexisting biological collection. SLE patients (n=165) were informed and did not objected, they were matched to healthy controls (n=48). Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 58 of 165 (35%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (p\<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, only the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p=0.0001). This association with renal involvement was higher with anti-ficolin-3 antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other traditional biomarker. These results suggest that anti-ficolin-3 could be useful for the diagnosis of active nephritis in SLE patients.	Lupus	À vérifier			À vérifier
Chronic speech BCIEighteen million people worldwide are affected by speech disorders. Locked-in syndrome (LIS) represents the most extreme form of communication disability resulting from motor impairment. In France, the Association du Locked-In Syndrome (ALIS) reports approximately 500 individuals with LIS, most of whom live at home. The quality of life of people with LIS depends strongly on their ability to communicate, and speech synthesis is the mode of communication restoration most desired by individuals with LIS. Several surveys have shown that improving communication abilities in these individuals leads to a significant improvement in their quality of life as well as that of their caregivers. Natural speech allows the production of an average of 150 words per minute. Non-invasive communication methods, whether based on residual motor function (eye-blink code) or on brain-machine or brain-computer interfaces (Brain-Computer Interface, BCI) using scalp electroencephalographic (EEG) signals, involve a high cognitive load and have low efficiency (spelling only a few letters per minute). Invasive BCIs for speech rehabilitation aim to overcome the limitations of non-invasive devices (cognitive overload and slow speech rate). The intention to act (the act of speaking) is predicted by an algorithm based on the direct decoding of neuronal activity from the sensorimotor cortex (the area where articulatory muscles are represented). To date, studies testing speech rehabilitation BCIs in humans remain rare. A subdural electrocorticographic (ECoG) invasive BCI enabled speech decoding (words and sentences from a limited repertoire) for chronic use (2 years). Real-time control of an on-screen cursor allowing spelling of up to 90 letters per minute (equivalent to text messaging) has also been achieved using an intracortical invasive BCI (Utah Array). Very recently, up to 60 words per minute were produced using an intracortical invasive BCI (Utah Array) implanted in the ventral premotor cortex, although with a connector potentially contaminated by acoustic audio feedback. Furthermore, these devices still rely on transcutaneous connectors, which may be sources of infection and prevent routine daily-life use. In summary, there is currently no fully implantable, wireless invasive "speech BCI" with real-time speech synthesis suitable for long-term home use. The present study will use an intracranial extradural invasive BCI combined with a speech synthesizer, with the aim of developing a communication tool suitable for everyday use. More specifically, the SpeechBCI protocol will propose two complementary BCI approaches in the same subject: a speech BCI (primary objective, BCI\_PAROLE device) and a cursor BCI (secondary objective). Both BCIs will use the WIMAGINE intracranial epidural system, enabling ECoG signal acquisition with a very limited risk of infection and brain injury and providing signals that are more stable over time compared with intracortical or subdural ECoG devices that retain transcutaneous connectors. These systems will allow long-term and ecological use, as the WIMAGINE implant is wireless and offers excellent long-term signal stability. The WIMAGINE implant has already been successfully tested for controlling an exoskeleton in a tetraplegic subject (operational for over 6 years) and very recently for controlling walking in real-life conditions via a spinal cord stimulator in a paraplegic individual. The BCI\_PAROLE device will integrate a speech synthesizer providing real-time auditory feedback to the speaker. The BCI-CURSEUR device will allow the subject to control an on-screen cursor to access various communication functionalities (web access, emails, chats, etc.). This will provide a complementary communication solution to real-time speech production. The hypothesis of this stydy is that the intention to speak (attempted speech) will be decoded by the BCI\_PAROLE device in individuals with LIS because, as with limb paralysis, paralysis of articulatory and phonatory muscles does not prevent the corresponding cortical map from producing specific signals. Similarly, the BCI-CURSEUR device will decode the intention to move a cursor and perform actions on a computer screen. Neuronal electrical signals will be recorded bilaterally from the ventral motor cortex (representation of lips, cheeks, tongue, palate, and larynx-the vocal tract) and from the dorsal part of the motor cortex (larynx and hand, the latter for controlling a two-degree-of-freedom cursor), using a total of 128 electrodes (64 on each cerebral hemisphere). The implant will be optimally positioned over speech motor areas using preoperative functional imaging in order to optimize speech decoding by the BCI\_PAROLE device.	Sclérose latérale amyotrophique	Non applicable	À vérifier	France	À vérifier
MY-EDUC — The Effectiveness of an ETP Programme in Myasthenia Gravis: a Proof-of-concept Study.CONTEXTE. Myasthenia gravis is a rare neuromuscular junction disorder affecting one in five thousand people (ORPHA 589). It is a chronic condition that progresses in episodes. Its severity varies, ranging from the invisible disability of fatigue to respiratory distress requiring intensive care. Currently, 270 patients with myasthenia gravis are being treated at Grenoble University Hospital in the Reference Centre for Rare Neuromuscular Diseases. The impact of this disease on quality of life is significant, and medication alone is not sufficient. However, to date, there are virtually no psychosocial interventions for patients with myasthenia gravis and no studies evaluating their effectiveness. In this context, the Cognitive Behavioural Stress Management (CBSM) programme is one of the stress management programmes applied to chronic health conditions whose effectiveness has already been demonstrated, particularly in terms of treatment adherence, quality of life, patients' coping strategies in the face of a chronic illness, and the outcomes of medical treatments (Antoni, 2003; Antoni et al., 2002, 2006). PRIMARY OBJECTIVE. Evaluation of the adaptation of an existing patient education programme, 'Living Better with Myasthenia', following the inclusion of an eight-session CBSM-based stress management module for adult patients living with myasthenia. METHODOLOGY (brief). Adaptation of the CBSM programme to the specific characteristics of myasthenia gravis: 1. Focus groups: exploration of beliefs associated with stress in myasthenia gravis. 2. DELPHI group: validation of the adaptation of the ETP programme 'Living better with myasthenia gravis' implemented at CHUGA following the inclusion of a stress management module (CBSM). Assessment of the feasibility of the MY-EDUC programme among groups of patients with myasthenia gravis. PRIMARY OUTCOME MEASURE. Comparison of levels of anxiety, depression (HADS), perceived stress (PSS) and quality of life (SF-36) as self-reported by patients enrolled in the programme before and after the MY-EDUC intervention. RESEARCH PROCEDURE. 1.1. FOCUS GROUPS. Expert patients and partner patients. They will be contacted via the list maintained by the rare disease healthcare network. 'General public' patients. A call for participants will be displayed in the CHUGA waiting room and circulated by partner organisations to their members. The study will be presented to expert and partner patients, as well as to "walk-in" patients in the focus groups, using the contact details on the "rare disease healthcare network" lists and via posters. An information leaflet outlining the study and its objectives will be provided to them. 1.2. FEASIBILITY AND ACCEPTABILITY STUDY OF THE MY-EDUC PROGRAMME. 1.2.1. Participant inclusion. Patient eligibility. The assessment of patient eligibility will be carried out by a specialist doctor from the CHUGA Rare Disease Centre of Excellence during a routine consultation with the patient (routine care). Participant inclusion. Once patient eligibility has been verified, the investigator from the CHUGA Rare Disease Centre, or a person to whom they have delegated this task, will contact the patient to invite them to participate in the MY-EDUC study. They will provide a verbal explanation of the study and hand over an information sheet during a follow-up consultation with the patient as part of routine care. If the patient volunteers to participate, they will give their consent to participate. The patient's consent will be recorded in the medical record. 1.2.2. Baseline assessment (T0). In the week leading up to the first session of the MY-EDUC programme, participants will complete the baseline assessment online (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes) with questionnaires presented in a randomised order. 1.2.3. Assessment during the intervention (T1). Based on repeated ecological measurements (Shiffman et al., 2008) via the study participants' mobile phones (two measurement points, before and after each session, randomly scheduled at least 36 hours apart, i.e. 16 measurements) using the free PielsSurvey software. 1.2.4. Final assessments (T2 and T3). Within one week of the final session of the MY-EDUC programme (T2: week 10 after T0), participants will complete a set of questionnaires electronically (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes), with the validated questionnaires presented in a randomised order.	Myasthénie	À vérifier	Traitement symptomatique		À vérifier
Anti-ficolin-3 Autoantibodies in Lupus NephritisSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, clinical data were obtained from medical files and blood samples were selected from preexisting biological collection. SLE patients (n=165) were informed and did not objected, they were matched to healthy controls (n=48). Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 58 of 165 (35%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (p\<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, only the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p=0.0001). This association with renal involvement was higher with anti-ficolin-3 antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other traditional biomarker. These results suggest that anti-ficolin-3 could be useful for the diagnosis of active nephritis in SLE patients.	Lupus	À vérifier			À vérifier
Chronic speech BCIEighteen million people worldwide are affected by speech disorders. Locked-in syndrome (LIS) represents the most extreme form of communication disability resulting from motor impairment. In France, the Association du Locked-In Syndrome (ALIS) reports approximately 500 individuals with LIS, most of whom live at home. The quality of life of people with LIS depends strongly on their ability to communicate, and speech synthesis is the mode of communication restoration most desired by individuals with LIS. Several surveys have shown that improving communication abilities in these individuals leads to a significant improvement in their quality of life as well as that of their caregivers. Natural speech allows the production of an average of 150 words per minute. Non-invasive communication methods, whether based on residual motor function (eye-blink code) or on brain-machine or brain-computer interfaces (Brain-Computer Interface, BCI) using scalp electroencephalographic (EEG) signals, involve a high cognitive load and have low efficiency (spelling only a few letters per minute). Invasive BCIs for speech rehabilitation aim to overcome the limitations of non-invasive devices (cognitive overload and slow speech rate). The intention to act (the act of speaking) is predicted by an algorithm based on the direct decoding of neuronal activity from the sensorimotor cortex (the area where articulatory muscles are represented). To date, studies testing speech rehabilitation BCIs in humans remain rare. A subdural electrocorticographic (ECoG) invasive BCI enabled speech decoding (words and sentences from a limited repertoire) for chronic use (2 years). Real-time control of an on-screen cursor allowing spelling of up to 90 letters per minute (equivalent to text messaging) has also been achieved using an intracortical invasive BCI (Utah Array). Very recently, up to 60 words per minute were produced using an intracortical invasive BCI (Utah Array) implanted in the ventral premotor cortex, although with a connector potentially contaminated by acoustic audio feedback. Furthermore, these devices still rely on transcutaneous connectors, which may be sources of infection and prevent routine daily-life use. In summary, there is currently no fully implantable, wireless invasive "speech BCI" with real-time speech synthesis suitable for long-term home use. The present study will use an intracranial extradural invasive BCI combined with a speech synthesizer, with the aim of developing a communication tool suitable for everyday use. More specifically, the SpeechBCI protocol will propose two complementary BCI approaches in the same subject: a speech BCI (primary objective, BCI\_PAROLE device) and a cursor BCI (secondary objective). Both BCIs will use the WIMAGINE intracranial epidural system, enabling ECoG signal acquisition with a very limited risk of infection and brain injury and providing signals that are more stable over time compared with intracortical or subdural ECoG devices that retain transcutaneous connectors. These systems will allow long-term and ecological use, as the WIMAGINE implant is wireless and offers excellent long-term signal stability. The WIMAGINE implant has already been successfully tested for controlling an exoskeleton in a tetraplegic subject (operational for over 6 years) and very recently for controlling walking in real-life conditions via a spinal cord stimulator in a paraplegic individual. The BCI\_PAROLE device will integrate a speech synthesizer providing real-time auditory feedback to the speaker. The BCI-CURSEUR device will allow the subject to control an on-screen cursor to access various communication functionalities (web access, emails, chats, etc.). This will provide a complementary communication solution to real-time speech production. The hypothesis of this stydy is that the intention to speak (attempted speech) will be decoded by the BCI\_PAROLE device in individuals with LIS because, as with limb paralysis, paralysis of articulatory and phonatory muscles does not prevent the corresponding cortical map from producing specific signals. Similarly, the BCI-CURSEUR device will decode the intention to move a cursor and perform actions on a computer screen. Neuronal electrical signals will be recorded bilaterally from the ventral motor cortex (representation of lips, cheeks, tongue, palate, and larynx-the vocal tract) and from the dorsal part of the motor cortex (larynx and hand, the latter for controlling a two-degree-of-freedom cursor), using a total of 128 electrodes (64 on each cerebral hemisphere). The implant will be optimally positioned over speech motor areas using preoperative functional imaging in order to optimize speech decoding by the BCI\_PAROLE device.	Sclérose latérale amyotrophique	Non applicable	À vérifier	France	À vérifier
MY-EDUC — The Effectiveness of an ETP Programme in Myasthenia Gravis: a Proof-of-concept Study.CONTEXTE. Myasthenia gravis is a rare neuromuscular junction disorder affecting one in five thousand people (ORPHA 589). It is a chronic condition that progresses in episodes. Its severity varies, ranging from the invisible disability of fatigue to respiratory distress requiring intensive care. Currently, 270 patients with myasthenia gravis are being treated at Grenoble University Hospital in the Reference Centre for Rare Neuromuscular Diseases. The impact of this disease on quality of life is significant, and medication alone is not sufficient. However, to date, there are virtually no psychosocial interventions for patients with myasthenia gravis and no studies evaluating their effectiveness. In this context, the Cognitive Behavioural Stress Management (CBSM) programme is one of the stress management programmes applied to chronic health conditions whose effectiveness has already been demonstrated, particularly in terms of treatment adherence, quality of life, patients' coping strategies in the face of a chronic illness, and the outcomes of medical treatments (Antoni, 2003; Antoni et al., 2002, 2006). PRIMARY OBJECTIVE. Evaluation of the adaptation of an existing patient education programme, 'Living Better with Myasthenia', following the inclusion of an eight-session CBSM-based stress management module for adult patients living with myasthenia. METHODOLOGY (brief). Adaptation of the CBSM programme to the specific characteristics of myasthenia gravis: 1. Focus groups: exploration of beliefs associated with stress in myasthenia gravis. 2. DELPHI group: validation of the adaptation of the ETP programme 'Living better with myasthenia gravis' implemented at CHUGA following the inclusion of a stress management module (CBSM). Assessment of the feasibility of the MY-EDUC programme among groups of patients with myasthenia gravis. PRIMARY OUTCOME MEASURE. Comparison of levels of anxiety, depression (HADS), perceived stress (PSS) and quality of life (SF-36) as self-reported by patients enrolled in the programme before and after the MY-EDUC intervention. RESEARCH PROCEDURE. 1.1. FOCUS GROUPS. Expert patients and partner patients. They will be contacted via the list maintained by the rare disease healthcare network. 'General public' patients. A call for participants will be displayed in the CHUGA waiting room and circulated by partner organisations to their members. The study will be presented to expert and partner patients, as well as to "walk-in" patients in the focus groups, using the contact details on the "rare disease healthcare network" lists and via posters. An information leaflet outlining the study and its objectives will be provided to them. 1.2. FEASIBILITY AND ACCEPTABILITY STUDY OF THE MY-EDUC PROGRAMME. 1.2.1. Participant inclusion. Patient eligibility. The assessment of patient eligibility will be carried out by a specialist doctor from the CHUGA Rare Disease Centre of Excellence during a routine consultation with the patient (routine care). Participant inclusion. Once patient eligibility has been verified, the investigator from the CHUGA Rare Disease Centre, or a person to whom they have delegated this task, will contact the patient to invite them to participate in the MY-EDUC study. They will provide a verbal explanation of the study and hand over an information sheet during a follow-up consultation with the patient as part of routine care. If the patient volunteers to participate, they will give their consent to participate. The patient's consent will be recorded in the medical record. 1.2.2. Baseline assessment (T0). In the week leading up to the first session of the MY-EDUC programme, participants will complete the baseline assessment online (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes) with questionnaires presented in a randomised order. 1.2.3. Assessment during the intervention (T1). Based on repeated ecological measurements (Shiffman et al., 2008) via the study participants' mobile phones (two measurement points, before and after each session, randomly scheduled at least 36 hours apart, i.e. 16 measurements) using the free PielsSurvey software. 1.2.4. Final assessments (T2 and T3). Within one week of the final session of the MY-EDUC programme (T2: week 10 after T0), participants will complete a set of questionnaires electronically (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes), with the validated questionnaires presented in a randomised order.	Myasthénie	À vérifier	Traitement symptomatique		À vérifier

Essais cliniques

3

Molécule	Indication / population	Phase	NCT	Titre	Statut
MY-EDUC — The Effectiveness of an ETP Programme in Myasthenia Gravis: a Proof-of-concept Study.	Myasthénie	À vérifier	NCT07512375	MY-EDUC — The Effectiveness of an ETP Programme in Myasthenia Gravis: a Proof-of-concept Study.	NOT_YET_RECRUITING
Chronic speech BCI	Sclérose latérale amyotrophique	Non applicable	NCT07698496	SpeechBCI — Evaluation of the Feasibility and Efficacy of a Chronic Brain-computer Interface for Speech Rehabilitation in Patients With Locked-in-syndrome (LIS)	NOT_YET_RECRUITING
Anti-ficolin-3 Autoantibodies in Lupus Nephritis	Lupus	À vérifier	NCT02625831	Anti-ficolin-3 Autoantibodies in Lupus Nephritis	COMPLETED

Publications

6

Molécule	Indication / population	Titre	Journal	Date
Chronic speech BCI		Initial experience with the precision neuroscience Layer 7 micro-electrocorticography interface for real-time intraoperative neural decoding.	Neurosurgical focus
Chronic speech BCI		Beyond the Air-Bone Gap: The Role of Bone Conduction Thresholds in Predicting Functional Outcomes and Guiding Surgical Decision-Making in Active Middle Ear and Bone Conduction Implants.	Audiology research
Chronic speech BCI		Management of conductive and mixed hearing loss intolerant to air-conduction hearing aids: A stepwise algorithm and narrative review from a Japanese perspective.	Auris, nasus, larynx
Anti-ficolin-3 Autoantibodies in Lupus Nephritis		Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus.	PloS one
Anti-ficolin-3 Autoantibodies in Lupus Nephritis		Autoantibodies Targeting Ficolin-2 in Systemic Lupus Erythematosus Patients With Active Nephritis.	Arthritis care & research
Anti-ficolin-3 Autoantibodies in Lupus Nephritis		Anti-Ficolin-2 and Anti-Ficolin-3 Autoantibody Detection by ELISA.	Methods in molecular biology (Clifton, N.J.)