The Use of LIFUP in Chronic Disorders of Consciousness

May 3, 2023 updated by: Caroline Schnakers, Casa Colina Hospital and Centers for Healthcare

Biomarkers of Thalamic LIFUP in Chronic Disorders of Consciousness

When patients survive a severe brain injury but fail to fully recover, they often enter a Disorder of Consciousness (DoC) --that is, a set of related conditions of decreased awareness and arousal including the Vegetative State (VS) and the Minimally Conscious State (MCS). When these conditions become chronic, there are no approved treatments to help bolster any further recovery. In prior work, we have shown the clinical feasibility and potential of Low Intensity Focused Ultrasound Pulsation (LIFUP) as a remarkably safe form of non-invasive brain stimulation in these conditions.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In the present study, we propose taking the "next step" to assess whether LIFUP can affect objective and validated markers of DoC patient impairment (in the direction of lesser impairment). Specifically, patients will be admitted at Casa Colina Hospital for a 10-day (in-patient) protocol, and two follow-up sessions, conducted remotely (e.g., over the phone) at 7 and 30-days post-discharge. The full length of the study is 40 days from admission. Over the admission period, patients will undergo multiple measurements of validated biomarkers, including behavioral testing, brain metabolism (using Positron Emission Tomography), and electroencephalography, before and after one session of LIFUP to thalamus.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • Pomona, California, United States, 91709
        • Casa Colina Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of VS or MCS based on the CRS-R .

  2. Chronic status:

    • 3 months post-injury for non-traumatic etiologies
    • 12 months post-injury for traumatic etiology
  3. 18 years of age or older.
  4. If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and the patient will be willing to remain on a stable regimen during the protocol.

Exclusion Criteria:

  1. History of neurological disorder (other than the brain injury).
  2. Unsuitability to undergo Magnetic Resonance (MR) assessment (e.g., non-MR compatible implants).
  3. Unsuitability to undergo LIFUP neuromodulation (e.g., presence of non-bone implant or absence of bone under the expected positioning of the device by the left temporal bone window).
  4. Manifest continuous spontaneous movement (which would prevent imaging)
  5. Participation in another concurrent clinical trial.
  6. Having undergone PET, CT, or other exam involving the use of ionizing radiation in the 12 months prior to the date of scheduled admission to Casa Colina.
  7. Dependence on ventilator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment LIFUP
LIFUP will be performed at the bedside using frameless stereotaxy. Specifically, the LIFUP transducer will be fit to the patient's head employing adjustable straps, and will be positioned over the patient's left temporal bone to minimize bone absorption and refraction. Accurate aiming will be ensured using the Brain Sight neuronavigation device, customized for tracking our LIFUP transducer. Following LIFUP, the patient will undergo a second EEG session, except for the EEG cap being fit to the patient's head prior to the LIFUP session so that, as soon as LIFUP administration is complete, the EEG paradigm can be promptly administered. The patient will then be allowed to rest (~1h).The patient will then be administered a second dose of tracer in order to undergo a second PET measurement. Finally, at the end-of-day, the clinical coordinator will collect an Adverse Event Questionnaire and will fit the PSG device for night monitoring.
Device: BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation
Administration of LIFUP will be performed at the bedside using frameless stereotaxy. Specifically, the LIFUP transducer will be fit to the patient's head employing adjustable straps, and will be positioned over the patient's left temporal bone, over the "temporal window" in order to minimize bone absorption and refraction. Accurate aiming will be ensured employing the BrainSight neuronavigation device, customized for tracking our LIFUP transducer (total ~10 min). Once satisfactory aiming is achieved, the LIFUP exposure will be initiated employing the settings described previously (which meet the FDA safety limits: ISPPA <= 190W/cm2, ISPTA <= 0.72W/cm2). Accurate aiming will be monitored in real-time throughout exposure using the Brain Sight Neuronavigation interface.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Coma Recovery Scale-Revised
Time Frame: Coma recovery scale-revised is completed at enrollment and twice a day on Day 1-10, except for Day 4. Maximum score is 23 with a minimum of 0. Higher scores mean better outcome.
Change in maximum total and subscale scores.
Coma recovery scale-revised is completed at enrollment and twice a day on Day 1-10, except for Day 4. Maximum score is 23 with a minimum of 0. Higher scores mean better outcome.
Electroencephalography
Time Frame: The EEG will be conducted at Day 3, 4, 7 and 10 of the study.
Change in fast to slow frequency power spectrum density and in P3b amplitude.
The EEG will be conducted at Day 3, 4, 7 and 10 of the study.
Positron Emission Tomography
Time Frame: This will be conducted on Day 4.
Assess change in local standard uptake value (SUV) and global SUV.
This will be conducted on Day 4.
Polysomnography
Time Frame: This will be conducted Day 1-10 of the study.
Change in nightly average density of sleep-spindles and sleep structure.
This will be conducted Day 1-10 of the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Casa Colina Hospital and Centers for Healthcare

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
UCLA Department of Psychology
Tiny Blue Dot INC.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Caroline Schnakers, PhD, Casa Colina Hospital and Centers for Healthcare
  • Principal Investigator: Martin Monti, PhD, UCLA Department of Psychology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 21, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 14, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 17, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2021

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB#21-000091

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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