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Arousal Pathways and Emergence From Sedation

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ClinicalTrials.gov Identifier: NCT02253758
Recruitment Status : Unknown
Verified September 2014 by michal roll, Tel-Aviv Sourasky Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : October 1, 2014
Last Update Posted : October 1, 2014
Sponsor:
Information provided by (Responsible Party):
michal roll, Tel-Aviv Sourasky Medical Center

Brief Summary:

Emergence from sedation involves an increase in both the level of consciousness and arousal. Some insight to the neural core of consciousness was gained in the recent past. Our research objective is to characterize for the first time the spatiotemporal mobilization of the ascending reticular activating system during emergence from sedation; stated otherwise - to capture the neural core of arousal.

To achieve this objective we plan to utilize the advanced imaging modality of EEG-fMRI. In short, volunteers will be placed in the MRI. Following baseline recordings they will be sedated with a continuous drip of propofol, titrated to deep sedation. Once in that sedation level, propofol administration will cease until emerging to an awake-calm/light sedation.

Continuous EEG recordings and fMRI scans will be taken, both task specific (auditory oddball) and resting-fMRI. Analyses will focus (but will not be restricted to) on constituents of the ascending reticular activating system.

The expected advances of this proposal are:

  1. Emergence from sedation (and anesthesia) is one of the critical stages and least elucidated area in the practice of anesthesia. Delayed awakening of varying degree is not uncommon after anesthesia and may have a number of different causes, individual or combined, which may be both drug or non-drug related, thus causing a diagnostic dilemma. Eventually - better insight into this subject will lead to better clinical practice and better understanding why patients emerge in such a diverse and sometimes unexpected manner.
  2. Knowledge of the internal structure underlying arousal from anesthesia will help develop / upgrade brain monitors that could tell the anesthesiologist the patient's level of consciousness and prediction of arousal.
  3. A detailed reproducible mapping of the arousal process may serve as the core of a drug screening platform for drugs that may expedite patient arousal.
  4. Elucidation of the arousal paradigm from sedation will enhance our knowledge of physiological sleep.

Research hypothesis

Return of consciousness is a complex phenomenon comprising of interplay between the cortex and deeper brain structures. We hypothesize that the activation signature is conserved and similar between subjects. Furthermore, we hypothesize that inter-subject variability will arise mainly in the time domain, as evident from the clinical observation of variable time to emergence in different patients.


Condition or disease Intervention/treatment Phase
Anesthesia Drug: Propofol Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Arousal Pathways and Emergence From Sedation
Study Start Date : October 2014
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol

Arm Intervention/treatment
Experimental: Sedation
Volunteers will be sedated to Ramsay score 4-5 with propofol, and data will be recorded during arousal
Drug: Propofol
Propofol will be injected as a continuous infusion by TCI intravenously
Other Name: Propofol Liporum 1%




Primary Outcome Measures :
  1. Characterization of brain network connectivity underlying arousal from anesthesia. [ Time Frame: Data collection time frame will not exceed one hour post propofol infusion cessation. ]
    Network connectivity of brain loci involved in arousal pathways will be evaluated for each patient at these time points: baseline, deep sedation and return to conscious state. The identification of these time points will be decided according to the Ramsay clinical scale for sedation depth. A score of 2 for baseline, 5 for deep sedation, and 2-3 for regaining consciousness. An external validation for these time points will derive from the oddball auditory test, in which the brain reaction to a sound in a different pitch is recorded. In the sedated state this reaction is perturbed.


Secondary Outcome Measures :
  1. Characterization of the internal structure and temporal hierarchy underlying arousal from anesthesia. [ Time Frame: Data collection time frame will not exceed one hour post propofol infusion cessation. ]
    At the group level an attempt will be made to discern temporal hierarchy (which of the aforementioned nuclei is the first to regain activity within the network) between the different ROIs (in voxels and normalized to a standarized brain) involved in the arousal pathways. The basal forebrain, laterodorsal tegmental nuclei, pedunculupontine nuclei, the ventral hypothalamus and the thalamus will all be included in the putative connectivity map.



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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males (ASA scale 1-2), volunteers only

Exclusion Criteria:

  • Use of chronic medications or illicit drugs
  • Metallic implants
  • Previous brain injury
  • General anaesthesia up to a week earlier to research examination
  • Known drug sensitivity to Propofol, soybean oil or peanuts

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02253758


Contacts
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Contact: Idit Matot, Prof. M.D. 97236974758 iditm@tlvmc.gov.il
Contact: Miri Davidovich 97236974758 mirid@tlvmc.gov.il

Locations
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Israel
Whol Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Contact: Talma Hendler, M.D. PhD    97236973094    hendlert@gmail.com   
Sub-Investigator: Talma Hendler, M.D. PhD         
Division of Anesthesia, Pain and Critical Care, Tel-Aviv Sourasky Medical Center
Tel-Aviv, Israel
Contact: Idit Matot, Prof. M.D.    97236974758    iditm@tlvmc.gov.il   
Contact: Miri Davidovich    97236974758    mirid@tlvmc.gov.il   
Principal Investigator: Idit Matot, Prof. M.D.         
Sub-Investigator: Tomer Nir, Resident         
Sponsors and Collaborators
Tel-Aviv Sourasky Medical Center
Investigators
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Principal Investigator: Idit Matot, Prof. M.D. Tel-Aviv Sourasky Medical Center
Publications:

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Responsible Party: michal roll, Dr. Michal Roll, Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier: NCT02253758    
Other Study ID Numbers: TASMC-14-IM-0383-CTIL
First Posted: October 1, 2014    Key Record Dates
Last Update Posted: October 1, 2014
Last Verified: September 2014
Keywords provided by michal roll, Tel-Aviv Sourasky Medical Center:
Magnetic Resonance Imaging
Electroencephalography
Conscious Sedation
Deep Sedation
Arousal
Consciousness
Additional relevant MeSH terms:
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Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics