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

Caregivers Clinical Trial

— PerBrain  

Official title:

A Multimodal Approach to Personalized Tracking of Evolving State-Of-Consciousness in Brain- Injured Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04798456
• Other study ID #: ERAPERMED2019-101 - PerBrain
• Secondary ID: 01KU2003
• Status: Recruiting
• Start date: June 1, 2020
• Est. completion date: June 2023

Study information

• Verified date: March 2021
• Source: Brain & Spine Institute (ICM)
• Contact: Jacobo Sitt, MD/PhD
• Phone: +33 (0)1 57 27 40 00
• Email: jacobo.sitt[@]icm-institute.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

• Recruitment is taking place in:

• France, Paris, Pitie-Salpetriere Hospital;

• Italy, Milan, Dipartimento di Cura e Riabilitazione delle Gravi Cerebrolesioni Acquisite (GCA);

• Israel, Raanana, Loewenstein Hospital;

• Germany, Munich: intensive care units of the University Clinic LMU Munich and Therapiezentrum Burgau

• 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)

Related Conditions & MeSH terms

• Caregivers
• Consciousness Disorders
• Disorders of Consciousness
• Minimally Conscious State
• Persistent Vegetative State
• Unresponsive Wakefulness Syndrome

Intervention

Behavioral:
• Coma scales
CRS-R and GOSE

Diagnostic Test:
• Imaging, electrophysiology, body signals, and brain stimulation
MRI, fMRI, EEG, TMS-EEG, Olfaction, Respiration, EKG

Behavioral:
• Questionnaires
several questionnaires and an interview with the caregiver

Locations

Country	Name	City	State
France	Paris Brain Institute (ICM)	Paris
Germany	University Hospital of the Ludwig-Maximilians-University of Munich	Munich
Israel	Loewenstein Hospital	Raanana
Italy	Dipartimento di Cura e Riabilitazione delle Gravi Cerebrolesioni Acquisite (GCA)	Milan

Sponsors (5)

Lead Sponsor	Collaborator
Brain & Spine Institute (ICM)	Fondazione Don Carlo Gnocchi Onlus, Ludwig-Maximilians - University of Munich, University of Milan, Weizmann Institute of Science

Countries where clinical trial is conducted

France,  Germany,  Israel,  Italy, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Caregivers: develop a brochure/guide to be applied in clinical practice for the effective communication of technology-based results	Working closely with Patient organizations/ patient representatives: Representatives of organizations ("Schädel- Hirnpatienten in Not e.V." in Germany) will be consulted in focus groups to jointly discuss the met and unmet needs and communication problems reported by caregivers in the study. Additionally, we will conduct a semi-structures interview with the caregivers. This information will help to devise with the research team effective communication strategies to be implemented in a brochure for the presentation of multimodal technology-based DOC testing.	12 months