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出境医 / 临床实验 / Recovery of Consciousness Following Intracerebral Hemorrhage (RECONFIG)

Recovery of Consciousness Following Intracerebral Hemorrhage (RECONFIG)

Study Description
Brief Summary:

The objectives of the RECONFIG clinical study are to :

  1. To identify the time to the first diagnosis of cognitive motor dissociation (CMD) in intracerebral hemorrhage (ICH) patients and to investigate whether these patients will clinically follow commands earlier after the hemorrhage.
  2. To determine whether CMD independently predicts long term functional outcomes (6-month mRS scores) in ICH patients, and is associated with long term cognitive and quality of life outcomes.
  3. To determine the EEG response to verbal commands of the motor imagery paradigm between patients with and without sensory aphasia.

The overall goal is to determine predictors and the trajectory of neurological recovery.


Condition or disease
Intra Cerebral Hemorrhage

Detailed Description:

Unconsciousness is common after an acute brain injury such as a brain hemorrhage, and recovery is poorly understood. This lack of knowledge is a key impediment to the development of novel strategies to improve outcomes and is one of the main reasons that prognostication of recovery of consciousness and functional outcomes is inaccurate. One-fifth of clinically unconscious patients with acute brain injury are able to follow commands using a simple, bedside EEG motor imagery test that directly measures brain activity associated with the attempt to move. This state is called cognitive motor dissociation (CMD). Pilot data indicate that CMD patients are more likely to clinically recover consciousness and have better longterm functional outcomes than non-CMD patients. To integrate these findings into clinical practice, there is a need to better understand the trajectory of CMD. This will only be possible in a tightly-controlled study with a homogenous patient cohort that is well characterized early after the injury and captures long-term outcomes.

RECONFIG is a multicenter, prospective, cross-sectional observational study in patients who have a clinical diagnosis of intracerebral hemorrhage and that are unresponsive at the time of enrollment. One hundred and fifty subjects will be recruited over 4 years at 2 sites. Subjects will be assessed with behavioral measures and MRI during the acute hospitalization. Patients will be followed for 6 months to determine the functional outcome (primary outcome measure). Additionally, the investigator will study conscious intracerebral hemorrhage patients with intracerebral hemorrhage and aphasia to determine the impact of aphasia.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Recovery of Consciousness Following Intracerebral Hemorrhage
Actual Study Start Date : June 15, 2019
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2024
Arms and Interventions
Group/Cohort
Primary ICH
Subject with acute brain injury will have data collected, including EEG, behavioral, clinical, and outcome measures.
Outcome Measures
Primary Outcome Measures :
  1. Time to clinical command following [ Time Frame: Hospital discharge (approximately 3 weeks) ]
    To investigate whether patients will clinically follow commands earlier after the hemorrhage.

  2. Modified Rankin Scale (mRS) Score [ Time Frame: 6 months ]
    A standardized interview that measures the degree of disability or dependence in the daily activities of people who have suffered causes of neurological disability. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.


Secondary Outcome Measures :
  1. Quality of Life in Neurological Disorders (Neuro-QoL T-score) [ Time Frame: 6 months ]

    Neuro-QoL is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. The T-score is the standardized score with a mean of 50 and a standard deviation of 10.

    For Neuro-QoL measures, higher scores equal more of the concept being measured (e.g., more Fatigue, more Lower Extremity Function - Mobility). Thus, a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.


  2. Difference in EEG response rate to verbal commands of the motor imagery paradigm. [ Time Frame: 6 months ]
    EEG response will be compared between patients with and without sensory aphasia.

  3. Modified Telephone Interview for Cognitive Status (TICS) score [ Time Frame: 6 months ]

    A standardized test of cognitive functioning that was developed for use in situations where in-person cognitive screening is impractical or inefficient. The 11 test items usually take less than 10 minutes to administer and score. All examinee responses are recorded verbatim. The individual item scores are summed to obtain the TICS Total score. The TICS Total score can be interpreted by means of four qualitative impairment ranges: Unimpaired, Ambiguous, Mildly Impaired, and Moderately to Severely Impaired.

    TICS Total score provides a measure of global cognitive functioning and can be used to monitor changes in cognitive functioning over time. Higher score represents less cognitive impairment.



Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Unresponsive and responsive patients diagnosed with ICH.
Criteria

Inclusion Criteria:

  • 18 years or older.
  • Diagnosis of primary ICH (i.e., related to hypertension or anticoagulants) on Head CT and/or MRI in the frontal lobe, thalamus, or striatocapsular region.
  • Unresponsive to commands within 48 hours after onset of the bleed.
  • English, Spanish or, French as the primary language.

Exclusion Criteria:

  • Major bleeding in the cortex outside of the frontal lobe, cerebellum, or brainstem (judged as a cause for unconsciousness as per the attending neurointensivist).
  • Other causes of ICH or different types of acute brain injury (e.g., traumatic brain injury).
  • Severe cardiorespiratory compromise and similar acutely life-threatening conditions at the time of enrollment.
  • Evidence of pre-morbid aphasia or deafness.
  • Unconscious prior to ICH.
  • Pregnancy.
  • Prisoners.
  • Health care proxy decides against study participation or decided for withdrawal of life sustaining therapies.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Jan Claassen, MD 212-305-7236 jc1439@cumc.columbia.edu
Contact: Angela Velazquez, MD 212-305-6071 agv2113@cumc.columbia.edu

Locations
Layout table for location information
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Jan Claassen, MD    212-305-7236    jc1439@cumc.columbia.edu   
Contact: Angela Velazquez, MD    212-305-6071    agv2113@cumc.columbia.edu   
Principal Investigator: Jan Claassen, MD         
Weill Cornell Medical Center Not yet recruiting
New York, New York, United States, 10065
Contact: Hooman Kamel, MD    212-746-0382    hok9010@med.cornell.edu   
Principal Investigator: Hooman Kamel, MD         
Sponsors and Collaborators
Columbia University
Pitié-Salpêtrière Hospital
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Jan Claassen, MD Associate Professor of Neurology
Tracking Information
First Submitted Date June 17, 2019
First Posted Date June 19, 2019
Last Update Posted Date July 18, 2019
Actual Study Start Date June 15, 2019
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 16, 2019)
  • Time to clinical command following [ Time Frame: Hospital discharge (approximately 3 weeks) ]
    To investigate whether patients will clinically follow commands earlier after the hemorrhage.
  • Modified Rankin Scale (mRS) Score [ Time Frame: 6 months ]
    A standardized interview that measures the degree of disability or dependence in the daily activities of people who have suffered causes of neurological disability. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.
Original Primary Outcome Measures
 (submitted: June 17, 2019)
  • Time to clinical command following [ Time Frame: Hospital discharge (approximately 3 weeks) ]
    To investigate whether patients will clinically follow commands earlier after the hemorrhage.
  • Modified Rankin Scale (mRS) Score [ Time Frame: 6 months ]
    A standardized interview that measures the degree of disability or dependence in the daily activities of people who have suffered causes of neurological disability. A 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.
Change History
Current Secondary Outcome Measures
 (submitted: July 16, 2019)
  • Quality of Life in Neurological Disorders (Neuro-QoL T-score) [ Time Frame: 6 months ]
    Neuro-QoL is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. The T-score is the standardized score with a mean of 50 and a standard deviation of 10. For Neuro-QoL measures, higher scores equal more of the concept being measured (e.g., more Fatigue, more Lower Extremity Function - Mobility). Thus, a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.
  • Difference in EEG response rate to verbal commands of the motor imagery paradigm. [ Time Frame: 6 months ]
    EEG response will be compared between patients with and without sensory aphasia.
  • Modified Telephone Interview for Cognitive Status (TICS) score [ Time Frame: 6 months ]
    A standardized test of cognitive functioning that was developed for use in situations where in-person cognitive screening is impractical or inefficient. The 11 test items usually take less than 10 minutes to administer and score. All examinee responses are recorded verbatim. The individual item scores are summed to obtain the TICS Total score. The TICS Total score can be interpreted by means of four qualitative impairment ranges: Unimpaired, Ambiguous, Mildly Impaired, and Moderately to Severely Impaired. TICS Total score provides a measure of global cognitive functioning and can be used to monitor changes in cognitive functioning over time. Higher score represents less cognitive impairment.
Original Secondary Outcome Measures
 (submitted: June 17, 2019)
  • Neuro-QoL T-score [ Time Frame: 6 months ]
    Neuro-QoL (Quality of Life in Neurological Disorders) is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. The T-score is the standardized score with a mean of 50 and a standard deviation of 10.
  • Difference in EEG response rate to verbal commands of the motor imagery paradigm. [ Time Frame: 6 months ]
    EEG response will be compared between patients with and without sensory aphasia.
  • Telephone Interview for Cognitive Status (TICS) score [ Time Frame: 6 months ]
    A standardized test of cognitive functioning that was developed for use in situations where in-person cognitive screening is impractical or inefficient. The 11 test items usually take less than 10 minutes to administer and score. All examinee responses are recorded verbatim. The individual item scores are summed to obtain the TICS Total score. The TICS Total score can be interpreted by means of four qualitative impairment ranges: Unimpaired, Ambiguous, Mildly Impaired, and Moderately to Severely Impaired.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Recovery of Consciousness Following Intracerebral Hemorrhage
Official Title Recovery of Consciousness Following Intracerebral Hemorrhage
Brief Summary

The objectives of the RECONFIG clinical study are to :

  1. To identify the time to the first diagnosis of cognitive motor dissociation (CMD) in intracerebral hemorrhage (ICH) patients and to investigate whether these patients will clinically follow commands earlier after the hemorrhage.
  2. To determine whether CMD independently predicts long term functional outcomes (6-month mRS scores) in ICH patients, and is associated with long term cognitive and quality of life outcomes.
  3. To determine the EEG response to verbal commands of the motor imagery paradigm between patients with and without sensory aphasia.

The overall goal is to determine predictors and the trajectory of neurological recovery.

Detailed Description

Unconsciousness is common after an acute brain injury such as a brain hemorrhage, and recovery is poorly understood. This lack of knowledge is a key impediment to the development of novel strategies to improve outcomes and is one of the main reasons that prognostication of recovery of consciousness and functional outcomes is inaccurate. One-fifth of clinically unconscious patients with acute brain injury are able to follow commands using a simple, bedside EEG motor imagery test that directly measures brain activity associated with the attempt to move. This state is called cognitive motor dissociation (CMD). Pilot data indicate that CMD patients are more likely to clinically recover consciousness and have better longterm functional outcomes than non-CMD patients. To integrate these findings into clinical practice, there is a need to better understand the trajectory of CMD. This will only be possible in a tightly-controlled study with a homogenous patient cohort that is well characterized early after the injury and captures long-term outcomes.

RECONFIG is a multicenter, prospective, cross-sectional observational study in patients who have a clinical diagnosis of intracerebral hemorrhage and that are unresponsive at the time of enrollment. One hundred and fifty subjects will be recruited over 4 years at 2 sites. Subjects will be assessed with behavioral measures and MRI during the acute hospitalization. Patients will be followed for 6 months to determine the functional outcome (primary outcome measure). Additionally, the investigator will study conscious intracerebral hemorrhage patients with intracerebral hemorrhage and aphasia to determine the impact of aphasia.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Unresponsive and responsive patients diagnosed with ICH.
Condition Intra Cerebral Hemorrhage
Intervention Not Provided
Study Groups/Cohorts Primary ICH
Subject with acute brain injury will have data collected, including EEG, behavioral, clinical, and outcome measures.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 17, 2019)
150
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 31, 2024
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 18 years or older.
  • Diagnosis of primary ICH (i.e., related to hypertension or anticoagulants) on Head CT and/or MRI in the frontal lobe, thalamus, or striatocapsular region.
  • Unresponsive to commands within 48 hours after onset of the bleed.
  • English, Spanish or, French as the primary language.

Exclusion Criteria:

  • Major bleeding in the cortex outside of the frontal lobe, cerebellum, or brainstem (judged as a cause for unconsciousness as per the attending neurointensivist).
  • Other causes of ICH or different types of acute brain injury (e.g., traumatic brain injury).
  • Severe cardiorespiratory compromise and similar acutely life-threatening conditions at the time of enrollment.
  • Evidence of pre-morbid aphasia or deafness.
  • Unconscious prior to ICH.
  • Pregnancy.
  • Prisoners.
  • Health care proxy decides against study participation or decided for withdrawal of life sustaining therapies.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Jan Claassen, MD 212-305-7236 jc1439@cumc.columbia.edu
Contact: Angela Velazquez, MD 212-305-6071 agv2113@cumc.columbia.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03990558
Other Study ID Numbers AAAS3574
1R01NS106014-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Jan Claassen, Columbia University
Study Sponsor Columbia University
Collaborators
  • Pitié-Salpêtrière Hospital
  • National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Jan Claassen, MD Associate Professor of Neurology
PRS Account Columbia University
Verification Date July 2019