Disorder of ConsciousnessNCT04921683
The Use of LIFUP in Chronic Disorders of Consciousness
A study testing BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation in people with Disorder of Consciousness and Vegetative State, run by Casa Colina Hospital and Centers for Healthcare at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disorder of Consciousness, Vegetative State, Minimally Conscious State
- What is being tested?
- BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2021to 14 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Disorder of Consciousness, Vegetative State, Minimally Conscious State, Minimally Conscious State Plus, Minimally Conscious State Minus, Traumatic Brain Injury
- Being tested
- BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation
- Medical subject headings
- Consciousness Disorders, Persistent Vegetative State, Brain Injuries, Traumatic, Stroke, Hypoxia, Brain, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound PulsationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment LIFUP | Experimental | 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. Receives: Device: BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coma Recovery Scale-Revised
Change in maximum total and subscale scores.
Measured: 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
Change in fast to slow frequency power spectrum density and in P3b amplitude.
Measured: The EEG will be conducted at Day 3, 4, 7 and 10 of the study.
Positron Emission Tomography
Assess change in local standard uptake value (SUV) and global SUV.
Measured: This will be conducted on Day 4.
Polysomnography
Change in nightly average density of sleep-spindles and sleep structure.
Measured: This will be conducted Day 1-10 of the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start21 Jun 2021
- Primary completion1 Mar 2023
- Study completion14 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Disorder of ConsciousnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Casa Colina Hospital and Centers for Healthcare
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles, Tiny Blue Dot Foundation
- Responsible party
- Principal investigator, Caroline Schnakers, Casa Colina Hospital and Centers for Healthcare
- Investigators
- Caroline Schnakers, PhD, Principal investigator, Casa Colina Hospital and Centers for HealthcareMartin Monti, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921683
- Sponsor's protocol ID
- IRB#21-000091
- Status last verified
- May 2023
- First submitted
- 17 May 2021
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 10869046Monti 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.
PubMed 27567470Monti 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.
PubMed 22224835Pasquinelli 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.
PubMed 31401074Schnakers 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.
PubMed 28901969Yoo 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.
PubMed 21876461
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Thalamic LIFUP in Chronic Disorders of Consciousness
- ClinicalTrials.gov ID
- NCT04921683
- Acronym / sponsor ID
- IRB#21-000091
- Conditions
- Disorder of Consciousness, Vegetative State, Minimally Conscious State, Minimally Conscious State Plus, Minimally Conscious State Minus, Traumatic Brain Injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Casa Colina Hospital and Centers for HealthcareUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, Tiny Blue Dot Foundation
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 14 Apr 2023 (actual)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment LIFUP | Experimental | Device: BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound PulsationLIFUP 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of VS or MCS based on the CRS-R .
- Chronic status:
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound PulsationAdministration 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. | Device | Treatment LIFUP |
Primary outcome
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.
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.
Positron Emission Tomography
Time frame: This will be conducted on Day 4.
Assess change in local standard uptake value (SUV) and global SUV.
Polysomnography
Time frame: This will be conducted Day 1-10 of the study.
Change in nightly average density of sleep-spindles and sleep structure.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Results publication: PubMed 10869046Adams 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 publication: PubMed 27567470Monti 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 publication: PubMed 22224835Monti 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 publication: PubMed 31401074Pasquinelli 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 publication: PubMed 28901969Schnakers 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 publication: PubMed 21876461Yoo 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caroline Schnakers, PhD principal investigator
Casa Colina Hospital and Centers for Healthcare
Martin Monti, PhD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation in people with Disorder of Consciousness and Vegetative State, run by Casa Colina Hospital and Centers for Healthcare at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04921683, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.