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The Use of LIFUP in Chronic Disorders of Consciousness

Primary Purpose

Disorder of Consciousness, Vegetative State, Minimally Conscious State

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation

About this trial

This is an interventional basic science trial for Disorder of Consciousness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of VS or MCS based on the CRS-R .
Chronic status:
- 3 months post-injury for non-traumatic etiologies
- 12 months post-injury for traumatic etiology
18 years of age or older.
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:

History of neurological disorder (other than the brain injury).
Unsuitability to undergo Magnetic Resonance (MR) assessment (e.g., non-MR compatible implants).
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).
Manifest continuous spontaneous movement (which would prevent imaging)
Participation in another concurrent clinical trial.
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.
Dependence on ventilator.

Sites / Locations

Casa Colina Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment LIFUP

Arm Description

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.

Outcomes

Primary Outcome Measures

Coma Recovery Scale-Revised

Change in maximum total and subscale scores.

Electroencephalography

Change in fast to slow frequency power spectrum density and in P3b amplitude.

Positron Emission Tomography

Assess change in local standard uptake value (SUV) and global SUV.

Polysomnography

Change in nightly average density of sleep-spindles and sleep structure.

Secondary Outcome Measures

Full Information

NCT ID

NCT04921683

First Posted

May 17, 2021

Last Updated

May 3, 2023

Sponsor

Casa Colina Hospital and Centers for Healthcare

Collaborators

UCLA Department of Psychology, Tiny Blue Dot INC.

1. Study Identification

Unique Protocol Identification Number

NCT04921683

Brief Title

The Use of LIFUP in Chronic Disorders of Consciousness

Official Title

Biomarkers of Thalamic LIFUP in Chronic Disorders of Consciousness

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

June 21, 2021 (Actual)

Primary Completion Date

March 1, 2023 (Actual)

Study Completion Date

April 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Casa Colina Hospital and Centers for Healthcare

Collaborators

UCLA Department of Psychology, Tiny Blue Dot INC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Disorder of Consciousness, Vegetative State, Minimally Conscious State, Minimally Conscious State Plus, Minimally Conscious State Minus, Traumatic Brain Injury, CVA (Cerebrovascular Accident), Anoxia, Brain, Thalamic Infarction, Coma; Prolonged

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

A single group model is when a group of subjects is administered treatment/exposure to device. Then it is measured and observed using behavioral and diagnostic tools over a specified amount of time throughout the study.

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment LIFUP

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Coma Recovery Scale-Revised

Description

Change in maximum total and subscale scores.

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.

Title

Electroencephalography

Description

Change in fast to slow frequency power spectrum density and in P3b amplitude.

Time Frame

The EEG will be conducted at Day 3, 4, 7 and 10 of the study.

Title

Positron Emission Tomography

Description

Assess change in local standard uptake value (SUV) and global SUV.

Time Frame

This will be conducted on Day 4.

Title

Polysomnography

Description

Change in nightly average density of sleep-spindles and sleep structure.

Time Frame

This will be conducted Day 1-10 of the study.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of VS or MCS based on the CRS-R . Chronic status: 3 months post-injury for non-traumatic etiologies 12 months post-injury for traumatic etiology 18 years of age or older. 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: History of neurological disorder (other than the brain injury). Unsuitability to undergo Magnetic Resonance (MR) assessment (e.g., non-MR compatible implants). 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). Manifest continuous spontaneous movement (which would prevent imaging) Participation in another concurrent clinical trial. 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. Dependence on ventilator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Caroline Schnakers, PhD

Organizational Affiliation

Casa Colina Hospital and Centers for Healthcare

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Martin Monti, PhD

Organizational Affiliation

UCLA Department of Psychology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Casa Colina Hospital

City

Pomona

State/Province

California

ZIP/Postal Code

91709

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

10869046

Citation

Adams JH, Graham DI, Jennett B. The neuropathology of the vegetative state after an acute brain insult. Brain. 2000 Jul;123 ( Pt 7):1327-38. doi: 10.1093/brain/123.7.1327.

Results Reference

result

PubMed Identifier

27567470

Citation

Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injury: A First-in-Man Report. Brain Stimul. 2016 Nov-Dec;9(6):940-941. doi: 10.1016/j.brs.2016.07.008. Epub 2016 Jul 22. No abstract available.

Results Reference

result

PubMed Identifier

22224835

Citation

Monti MM. Cognition in the vegetative state. Annu Rev Clin Psychol. 2012;8:431-54. doi: 10.1146/annurev-clinpsy-032511-143050. Epub 2012 Jan 3.

Results Reference

result

PubMed Identifier

31401074

Citation

Pasquinelli C, Hanson LG, Siebner HR, Lee HJ, Thielscher A. Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Brain Stimul. 2019 Nov-Dec;12(6):1367-1380. doi: 10.1016/j.brs.2019.07.024. Epub 2019 Jul 31.

Results Reference

result

PubMed Identifier

28901969

Citation

Schnakers C, Monti MM. Disorders of consciousness after severe brain injury: therapeutic options. Curr Opin Neurol. 2017 Dec;30(6):573-579. doi: 10.1097/WCO.0000000000000495.

Results Reference

result

PubMed Identifier

21876461

Citation

Yoo SS, Kim H, Min BK, Franck E, Park S. Transcranial focused ultrasound to the thalamus alters anesthesia time in rats. Neuroreport. 2011 Oct 26;22(15):783-7. doi: 10.1097/WNR.0b013e32834b2957.

Results Reference

result

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The Use of LIFUP in Chronic Disorders of Consciousness

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