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

NCT04798456 | Unknown

• 2 other identifiers: ERAPERMED2019-101 - PerBrain01KU2003
• Study Type: observational
• Target: 150
• Locations: 4 countries
• Sites: 4

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

Keywords

Clinical Neuroscience; Disorders of Consciousness; Neuroimaging; Brain-Body interactions; Multimodal precision diagnosis; Machine Learning; Caregivers well-being; Unresponsive wakefulness syndrome; Minimally conscious state

Outcome Measures

Primary Outcomes (14)

• Patients: Implementation of a hierarchical multi-modal personalized procedure to diagnose and track the change of the state of consciousness in brain-injured patients

  Coma Recovery Scale Revised (CRS-R) \[0-23\] Higher score better outcome

  Changes from T1: 1-2 Months from injury; T2: 4-7 Months from injury; T3: 9-12 months from injury

• Patients: Implementation of a hierarchical multi-modal personalized procedure to diagnose and track the change of the state of consciousness in brain-injured patients

  Extended Glasgow Outcome Scale (GOSE) \[1-8\] Higher score better outcome

  Changes from T1: 1-2 Months from injury; T2: 4-7 Months from injury; T3: 9-12 months from injury

• Patients: Implementation of a hierarchical multi-modal personalized procedure to diagnose and track the change of the state of consciousness in brain-injured patients

  Quantitative high density EEG (64 Electrodes)

  Changes from T1: 1-2 Months from injury; T2: 4-7 Months from injury; T3: 9-12 months from injury

• Patients: Implementation of a hierarchical multi-modal personalized procedure to diagnose and track the change of the state of consciousness in brain-injured patients

  Standard EEG and transcranial magnetic stimulation (TMS-EEG)

  Changes from T1: 1-2 Months from injury; T2: 4-7 Months from injury; T3: 9-12 months from injury

• Patients: Implementation of a hierarchical multi-modal personalized procedure to diagnose and track the change of the state of consciousness in brain-injured patients

  Structural MRI and functional MRI (without contrast agent)

  Changes from T1: 1-2 Months from injury; T2: 4-7 Months from injury; T3: 9-12 months from injury

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Sociodemographic characteristics

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Brief Illness Perception Questionnaire (BIPQ) \[0-80\] Higher score more positive illness representation

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Euro-Qol 5 (EQ-5D61) \[0-15\] higher values indicating better perceived quality of life.

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Adult Carer Quality of Life Questionnaire (ACQoL24) \[0-120\] higher values better quality of life

  Changes from 0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Hospital Anxiety and Depression Scale (HADS) \[0-52\] higher scores indicating higher levels of anxiety and depression.

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Resilience (RS14) \[14-98\] higher scores relate to higher resilience levels.

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Sense of coherence (SOCS) \[13-91\] higher scores indicate higher sense of coherence.

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Treatment choices survey \[28-140\] higher score indicates a stronger agreement with the treatment and higher reason to take a given treatment decision

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

• Caregivers: use of questionnaires to asses change in factors that impact well-being and treatment decisions of informal caregivers/family members confronted with multimodal technology-based tests for DoC patients

  Semi-structured qualitative Interview based on a thematic grid for brochure development

  Changes from C0: before T1 (1-2 Months from injury); C1: between T1(1-2 Months from injury) and T2 (4-7 Months from injury); C2: between T2 (4-7 Months from injury) and T3 (9-12 Months from injury); C3: after T3 (9-12 Months from injury)

Secondary Outcomes (1)

• Caregivers: develop a brochure/guide to be applied in clinical practice for the effective communication of technology-based results

  12 months

Study Arms (2)

Patients with DoC

Behavioral: Coma scales; Diagnostic Test: Imaging, electrophysiology, body signals, and brain stimulation

Caregivers/ legal guardian of patients with DoC

Behavioral: Questionnaires

Interventions

Coma scales BEHAVIORAL

CRS-R and GOSE

Patients with DoC

Imaging, electrophysiology, body signals, and brain stimulation DIAGNOSTIC_TEST

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

Patients with DoC

Questionnaires BEHAVIORAL

several questionnaires and an interview with the caregiver

Caregivers/ legal guardian of patients with DoC

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

intensive care units and rehabilitation centres

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Paris Brain Institute (ICM): lead
• University of Milan: collaborator
• Fondazione Don Carlo Gnocchi Onlus: collaborator
• Weizmann Institute of Science: collaborator
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (4)

Paris Brain Institute (ICM)

Paris, 75013, France

RECRUITING

University Hospital of the Ludwig-Maximilians-University of Munich

Munich, 81377, Germany

RECRUITING

Loewenstein Hospital

Raanana, 43100, Israel

RECRUITING

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

Milan, Italy

RECRUITING

Related Publications (8)

• Giacino JT, Kalmar K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):166-74. doi: 10.1080/09602010443000498.

  PMID: 16350959 BACKGROUND

• 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.

  PMID: 28892566 BACKGROUND

• Arzi A, Rozenkrantz L, Gorodisky L, Rozenkrantz D, Holtzman Y, Ravia A, Bekinschtein TA, Galperin T, Krimchansky BZ, Cohen G, Oksamitni A, Aidinoff E, Sacher Y, Sobel N. Olfactory sniffing signals consciousness in unresponsive patients with brain injuries. Nature. 2020 May;581(7809):428-433. doi: 10.1038/s41586-020-2245-5. Epub 2020 Apr 29.

  PMID: 32461641 BACKGROUND

• Casali AG, Gosseries O, Rosanova M, Boly M, Sarasso S, Casali KR, Casarotto S, Bruno MA, Laureys S, Tononi G, Massimini M. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Transl Med. 2013 Aug 14;5(198):198ra105. doi: 10.1126/scitranslmed.3006294.

  PMID: 23946194 BACKGROUND

• 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.

  PMID: 30285102 BACKGROUND

• 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.

  PMID: 24945467 BACKGROUND

• Derchi CC, Comanducci A, Bassi M, Rosenfelder MJ, Valota C, Willacker L, Oehl P, Rosanova M, Sitt JD, Bender A, Kuehlmeyer K. Surrogate decision-making for people with disorders of consciousness: considering the control-preferences of informal caregivers before implementing multimodal testing. BMC Med Ethics. 2026 Jan 2. doi: 10.1186/s12910-025-01357-4. Online ahead of print.

  PMID: 41484601 DERIVED

• 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.

  PMID: 36494776 DERIVED

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State

Interventions

Diagnostic Imaging; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Central Study Contacts

Jacobo Sitt, MD/PhD

CONTACT

+33 (0)1 57 27 40 00; jacobo.sitt@icm-institute.org

Benjamin Rohaut, MD/PhD

CONTACT

+33 (0)1 57 27 40 00; benjamin.rohaut@icm-institute.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Director, INSERM

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 15, 2021
• Study Start: June 1, 2020
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: March 15, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); IL (1); IT (1); DE (1)