Aiming for a Better Understanding and Improvement of the Diagnosis and Prognosis of Patients With Disorders of Consciousness Through Multimodal Observations

NCT ID: NCT04798456

Last Updated: 2021-03-15

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2023-06-30

Brief Summary

Improved treatment of severe brain injuries has resulted in increased survival rates. While some of these patients regain consciousness after a transient state of coma, others may develop a disorder of consciousness (DoC). Diagnosis of DoC currently relies on standardized behavioral assessment. The importance of accuracy in such diagnosis cannot be overstated, as it guides critical decisions on treatment (including pain management), and could underlie end-of-life decisions. Despite this importance, current behavioral diagnosis often fails, if because of the major sensory and motor deficits associated with DoC, or because of the heterogeneous etiology and pathophysiology associated with the condition. Finally, the need for accurate diagnosis and prognosis transcends the needs of the patients alone: caregiving of these patients is very stressful, principally for the large uncertainty associated with them. Thus, more accurate diagnosis and prognosis provide major relief for caregivers, and paradoxically, even if the news is not "good". For all these reasons it is critical to developing personalized diagnosis and prognosis prediction tools that permit a stratified analysis at the single-patient level. The PerBrain Project will benefit from the multidisciplinary partners' expertise, and the unique opportunity to perform longitudinal assessments in four clinical sites through both established and novel electrophysiological, neuroimaging, and physiological techniques. Based on the collected data, the investigators will develop a multimodal personalized diagnostic tool for DoC patients using state-of-the-art computational tools, such as machine learning, in order to better determine the current state (diagnosis) and future outcome (prognosis). The overall aim of this project will provide for a better understanding of the pathophysiological mechanisms in DoC, which will, in turn, allow personalized rehabilitation strategies, and improved single-patient predictions of state and prognosis.

Conditions

Disorders of Consciousness; Minimally Conscious State; Unresponsive Wakefulness Syndrome; Caregivers

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with DoC

Coma scales

Intervention Type: BEHAVIORAL

CRS-R and GOSE

Imaging, electrophysiology, body signals, and brain stimulation

Intervention Type: DIAGNOSTIC_TEST

MRI, fMRI, EEG, TMS-EEG, Olfaction, Respiration, EKG

Caregivers/ legal guardian of patients with DoC

Questionnaires

Intervention Type: BEHAVIORAL

several questionnaires and an interview with the caregiver

Interventions

Coma scales

CRS-R and GOSE

Intervention Type: BEHAVIORAL

Imaging, electrophysiology, body signals, and brain stimulation

MRI, fMRI, EEG, TMS-EEG, Olfaction, Respiration, EKG

Intervention Type: DIAGNOSTIC_TEST

Questionnaires

several questionnaires and an interview with the caregiver

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Disorder of consciousness (UWS and MCS) patients and their caregiver/legal guardian
• Patient age: 18-85 years
• Informed consent signed by legal guardian

Exclusion Criteria

• Pregnancy
• Pre-existing coma/VS/MCS
• Continuous medical sedation (induced coma)
• Use of barbiturates for sedation
• Terminal malignant disease, as it increases the likelihood of not being alive for the 12-month follow-up
• Prediction of a highly unlikely survival until the time of the 12-month follow-up due to conditions such as multi-organ failure based on the judgement of a critical care physician
• Withdrawal of life-support
• Palliative care setting
• Epileptic seizures (TMS contraindication)
• MRI contraindications (magnetic material in or on person such as pacemakers, cochlear implants, shell splinters, metal plates, certain prosthetic joints/limbs, copper-based intrauterine device, magnetic clips or stents, some large tattoos)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Milan

OTHER

Sponsor Role: collaborator

Fondazione Don Carlo Gnocchi Onlus

OTHER

Sponsor Role: collaborator

Weizmann Institute of Science

OTHER

Sponsor Role: collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

Paris Brain Institute (ICM)

OTHER

Sponsor Role: lead

Responsible Party

Jacobo Sitt

Research Director, INSERM

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Paris Brain Institute (ICM)

Paris, , France

Site Status: RECRUITING

University Hospital of the Ludwig-Maximilians-University of Munich

Munich, , Germany

Site Status: RECRUITING

Loewenstein Hospital

Raanana, , Israel

Site Status: RECRUITING

Dipartimento di Cura e Riabilitazione delle Gravi Cerebrolesioni Acquisite (GCA)

Milan, , Italy

Site Status: RECRUITING

Countries

France; Germany; Israel; Italy

Central Contacts

Jacobo Sitt, MD/PhD

Role: CONTACT

jacobo.sitt@icm-institute.org

+33 (0)1 57 27 40 00

Benjamin Rohaut, MD/PhD

Role: CONTACT

benjamin.rohaut@icm-institute.org

+33 (0)1 57 27 40 00

Facility Contacts

Jacobo Sitt, MD/PhD

Role: primary

jacobo.sitt@icm-institute.org

Benjamin Rohaut, MD/PhD

Role: backup

benjamin.rohaut@icm-institute.org

Andreas Bender, MD/Prof

Role: primary

andreas.bender@med.uni-muenchen.de

Theresa Raiser, PhD

Role: backup

theresa.raiser@med.uni-muenchen.de

Noam Sobel, Prof

Role: primary

noam.sobel@weizmann.ac.il

Danielle Honigstein, PhD

Role: backup

danielle.honigstein@weizmann.ac.il

Angela Comanducci, MD

Role: primary

acomanducci@dongnocchi.it

References

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Reference Type: BACKGROUND

PMID: 16350959 (View on PubMed)

Raimondo F, Rohaut B, Demertzi A, Valente M, Engemann DA, Salti M, Fernandez Slezak D, Naccache L, Sitt JD. Brain-heart interactions reveal consciousness in noncommunicating patients. Ann Neurol. 2017 Oct;82(4):578-591. doi: 10.1002/ana.25045. Epub 2017 Oct 11.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Engemann DA, Raimondo F, King JR, Rohaut B, Louppe G, Faugeras F, Annen J, Cassol H, Gosseries O, Fernandez-Slezak D, Laureys S, Naccache L, Dehaene S, Sitt JD. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain. 2018 Nov 1;141(11):3179-3192. doi: 10.1093/brain/awy251.

Reference Type: BACKGROUND

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Vogler J, Klein AM, Bender A. Long-term health-related quality-of-life in patients with acquired brain injury and their caregivers. Brain Inj. 2014;28(11):1381-8. doi: 10.3109/02699052.2014.919536. Epub 2014 Jun 19.

Reference Type: BACKGROUND

PMID: 24945467 (View on PubMed)

Willacker L, Raiser TM, Bassi M, Bender A, Comanducci A, Rosanova M, Sobel N, Arzi A, Belloli L, Casarotto S, Colombo M, Derchi CC, Flo Rama E, Grill E, Hohl M, Kuehlmeyer K, Manasova D, Rosenfelder MJ, Valota C, Sitt JD. PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study. BMC Neurol. 2022 Dec 9;22(1):468. doi: 10.1186/s12883-022-02958-x.

Reference Type: DERIVED

PMID: 36494776 (View on PubMed)

Other Identifiers

01KU2003

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ERAPERMED2019-101 - PerBrain

Identifier Type: -

Identifier Source: org_study_id