Prognostic Factors to Regain Consciousness

Investigation of Prognostic Factors to Regain Consciousness in Neurological Early Rehabilitation

The study aims to identify factors that predict the medium and long-term outcome of patients with disorders of consciousness (DOC) undergoing early neurological rehabilitation.

In this prospective, observational study, 130 DOC patients are going to be included (36 months). At study entry, different routine data, disease severity and functional status are documented for each patient. In addition, MRI, EEG and evoked potentials are measured within the first week. The level of consciousness is recorded with the Coma-Recovery-Scale-Revised and serves as the primary outcome parameter. Complications, comorbidities, functional status and leve of consciousness are assessed weekly. After eight weeks, the measurement of the MRI, the EEG and the evoked potentials are repeated. After 3, 6 and 12 months, the Glasgow Outcome Scale-Revised is used to followed up the current status of the patients.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Traumatic Brain Injury; Neurologic Disorder; Disorder of Consciousness; Hypoxic-Ischemic Encephalopathy
• Intervention / Treatment: Diagnostic test: Coma-Recovery-Scale-Revised (CRS-R)

Detailed Description

Due to continuous improvements in acute medical care, the number of patients surviving severe brain damage has increased over the past decades. While some patients improve significantly during the first days after the injury, other patients remain in altered states of consciousness (i.e. coma, unresponsive wakefulness syndrome or minimally conscious state). Acquired brain damage such as cerebrovascular diseases, traumatic brain injuries or hypoxic-ischemic encephalopathies are the main causes of severe impaired consciousness.The correct classification of the level of consciousness is of great importance, since the different states of consciousness are associated with different prognoses and treatment options. Patients who show minimal signs of consciousness (MCS) a month after the onset of the disease have better chances of regaining consciousness within one year than UWS patients. Within both categories (UWS, MCS), traumatic aetiologies in turn have a better prognosis than non-traumatic aetiologies. The prognosis usually begins with the admission of the patients to the intensive care unit of the acute care facility. But even in later treatment phases, a large number of patients regain consciousness, e.g. during post-acute early rehabilitation and even years after the disease. Numerous factors are associated with the prognosis (e.g. age, aetiology, duration of illness, functional status and state of consciousness). Although there are numerous studies on the prognostic factors and outcome of patients with severe brain damage, only a few have explicitly examined patients with initially severe and long-lasting impaired consciousness. The study therefore aims to identify factors that predict the medium and long-term outcome of patients with severe impaired consciousness in early neurological rehabilitation.

Over a period of 36 months, 130 patients undergoing neurological early rehabilitation with impaired consciousness are included. It is a prospective observational study that is carried out in a single neurological rehabilitation centre (monocentric). Different routine data, disease severity and functional status are documented for each patient. In addition, MRI, EEG and evoked potentials are measured within the first week. The level of consciousness is recorded with the Coma-Recovery-Scale-Revised and serves as the primary outcome parameter. Complications, comorbidities, functional status and leve of consciousness are assessed weekly. After eight weeks, the measurement of the MRI, the EEG and the evoked potentials are repeated. After 3, 6 and 12 months, the Glasgow Outcome Scale-Revised is used to follow up the current status of the patients.

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Melanie Boltzmann, PhD; Phone Number: 0049 5152 781 256; Email: m.boltzmann@bdh-klinik-hessisch.oldendorf
• Study Contact Backup: Name: Simone B Schmidt, PhD; Phone Number: 0049 5152 781 215; Email: si.schmidt@bdh-klinik-hessisch.oldendorf

Study Locations

• Germany
  • Hessisch Oldendorf, Germany, 31840
    • Recruiting
    • BDH-Clinic Hessisch Oldendorf
    • Contact: Melanie Boltzmann, PhD; Phone Number: 0049 5152 781 256; Email: m.boltzmann@bdh-klinik-hessisch-oldendorf.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients undergoing neurological early rehabilitation with impaired consciousness and admitted to intensive care unit

Description

Inclusion Criteria:

• early neurological rehabilitation (phase B)
• stroke, traumatic brain injury, hypoxic-ischemic encephalopathy
• disorder of consciousness (coma, UWS, MCS)
• at minimum two weeks after disease onset
• admission to intensive care unit
• written consent from the patient's legal representative
• exclusion of pregnancy

Exclusion Criteria:

• insufficient cardiorespiratory stability
• fractures or severe infratentorial brain injuries leading to impaired auditory evoked - potentials
• previous brain damage
• mental disorders (dementia, depression)
• colonization with multi-resistant pathogens
• MRI contraindications
• claustrophobia
• weight > 120 kg

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICU patients; Patients with impaired consciousness admitted to intensive care unit after severe brain injury	Diagnostic test: Coma-Recovery-Scale-Revised (CRS-R); CRS-R assessments (15 minutes) are repeated weekly after study entry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changed functional status	Functional status is measured with Early Rehabilitation Barthel Index (ERBI; Range: -325 to 100; higher scores mean a better outcome) weekly.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changed level of consciousness	Level of consciousness is measured with the Coma-Recovery-Scale-Revised (CRS-R; Range: 0 to 23; higher scores mean a better outcome) weekly.	8 weeks
Duration until consciousness is regained	Time until patients show first signs of consciousness	up to 8 weeks

Collaborators and Investigators

• Sponsor: BDH-Klinik Hessisch Oldendorf
• Investigators: Study Director: Jens D Rollnik, MD, BDH-Clinic Hessisch Oldendorf; Principal Investigator: Melanie Boltzmann, PhD, BDH-Clinic Hessisch Oldendorf

Publications and helpful links

General Publications

• Lucca LF, Lofaro D, Pignolo L, Leto E, Ursino M, Cortese MD, Conforti D, Tonin P, Cerasa A. Outcome prediction in disorders of consciousness: the role of coma recovery scale revised. BMC Neurol. 2019 Apr 18;19(1):68. doi: 10.1186/s12883-019-1293-7.
• Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C; Intensive Rehabilitation Unit Study Group of the IRCCS Don Gnocchi Foundation, Italy. Improvement on the Coma Recovery Scale-Revised During the First Four Weeks of Hospital Stay Predicts Outcome at Discharge in Intensive Rehabilitation After Severe Brain Injury. Arch Phys Med Rehabil. 2018 May;99(5):914-919. doi: 10.1016/j.apmr.2018.01.015. Epub 2018 Feb 8.
• Portaccio E, Morrocchesi A, Romoli AM, Hakiki B, Taglioli MP, Lippi E, Di Renzone M, Grippo A, Macchi C. Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge in intensive rehabilitation after severe brain injury. Brain Inj. 2018;32(6):730-734. doi: 10.1080/02699052.2018.1440420. Epub 2018 Feb 26.
• Estraneo A, Moretta P, Loreto V, Lanzillo B, Cozzolino A, Saltalamacchia A, Lullo F, Santoro L, Trojano L. Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Neurology. 2013 Jan 29;80(5):464-70. doi: 10.1212/WNL.0b013e31827f0f31. Epub 2013 Jan 9.
• Estraneo A, Moretta P, Loreto V, Lanzillo B, Santoro L, Trojano L. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology. 2010 Jul 20;75(3):239-45. doi: 10.1212/WNL.0b013e3181e8e8cc. Epub 2010 Jun 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Prognosis; Outcome; Neurological rehabilitation; Level of consciousness
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Ischemia; Signs and Symptoms, Respiratory; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Hypoxia, Brain; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries, Traumatic; Stroke; Nervous System Diseases; Hypoxia-Ischemia, Brain; Consciousness Disorders
• Other Study ID Numbers: DOC-OUT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication.
• IPD Sharing Time Frame: Period of availability begins when results are published, at the earliest in Dec 2023
• IPD Sharing Access Criteria: IPD can be obtained from the principal investigator upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No