Consciousness DisordersLIFUPNCT02522429
Thalamic Low Intensity Focused Ultrasound in Brain Injury
A study testing Low Intensity Focused Ultrasound Device in people with Consciousness Disorders and Brain Injuries, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness. To date there exists no standard intervention for patients suffering from these devastating conditions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Consciousness Disorders, Brain Injuries
- What is being tested?
- Low Intensity Focused Ultrasound Device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2016to 3 Nov 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Acute patients
- < 6 weeks since injury
- a Glasgow Coma Score < 9 (at the time of injury)
- an abnormal CT
- prolonged loss of consciousness (>24h)
- behavioral profile consistent with a VS or MCS as assessed with the Coma Recovery Scale Revised.
Show all 9Show fewer
- Chronic patients:
- > 3 months post injury for non-traumatic injuries, >12 months post-injury for traumatic injuries
- behavioral profile consistent with a VS or MCS as assessed with the Coma Recovery Scale Revised.
Who cannot join
- deep sedation
- history of neurological illness prior to injury
- inability to safely enter the MR environment (e.g., ferromagnetic non MR safe implants)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095-1563
About this study
Official title: Thalamic Low Intensity Focused Ultrasound Stimulation in Disorders of Consciousness Following Severe Brain Injury
Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness. To date there exists no standard intervention for patients suffering from these devastating conditions. The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for those patients. In this study, LIFUP will be performed during two sessions. The proposed experiment will involve behavioral and paramedical measurements just before and after each of the two LIFUP sessions in a small sample of patients (up to 15 acute and 15 chronic patients) in order to evaluate the feasibility of a full scale clinical trial.
Read the detailed description
Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness (DOC). Typically developed after severe brain injury, this set of related conditions includes Coma, the Vegetative State (VS) and the Minimally Conscious State (MCS). In the past 20 years, an increasing amount of research has broken many conventions about these disorders, including the once widespread belief that these patients are entirely apallic - that is, lack any kind of "higher" activity. Since then, it has been shown that a lot of brain activity, including relatively high-level cognitive processes, can remain in DOC patients. Nonetheless, to date there exists no standard intervention for patients suffering from these devastating conditions. Developing interventions for this population is extremely important first and foremost for the well-being of patients, who - today - remain completely dependent on assisted care, are often unable to participate in rehabilitative programs because of their lack of behavioral responsiveness, and thus find themselves prisoners of a condition characterized by uncertainty at the medical, legal and ethical decision-making levels. In addition, these conditions, which can last indefinitely, also place great emotional and monetary strain on families, large burdens on care-takers - often leading to increased rates of burn-out - and large financial stress on medical structures and public finances due to the large costs imposed by prolonged intensive care.
The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for patients with severe brain injury.
LIFUP will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session) in a small sample of patients (up to 15 acute and 15 chronic DOC patients) in order to evaluate the feasibility of a full scale clinical trial.
The duration of participation in the study will be a year. In terms of impact, we think this project would have a number of immediate consequences. (i) A successful pilot study and any indication that this approach might have the hypothesized effect would place us in a unique position to initiate a fully-fledged double-blind clinical trial in a large cohort of patients.
(ii) From a purely scientific point of view, by virtue of testing what is today the most prominent physiological hypothesis concerning loss and recovery of consciousness after severe brain injury, this project has a direct repercussion on our understanding of the mechanisms underlying these conditions. (iii) From a clinical and patient management point of view the present project is the first necessary step towards opening a completely new avenue for care-taking in patients suffering from this devastating condition for which there is no intervention. In particular, if this project were successful in the long run (e.g., after a double-blind full clinical trial), it could make widely available a non-invasive protocol which could substitute the currently highly invasive (and therefore not widely available, and high risk) only intervention available.
- Conditions
- Consciousness Disorders, Brain Injuries
- Being tested
- Low Intensity Focused Ultrasound Device
- Medical subject headings
- Consciousness Disorders, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Intensity Focused Ultrasound DeviceDevice
Also called BX Pulsar 1001, BX Pulsar 1002
Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI and EEG) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
| Study group | Role | What they receive |
|---|---|---|
| Low Intensity Focused Ultrasound Device | Experimental | 15 acute DOC patients, 15 chronic DOC patients Receives: Device: Low Intensity Focused Ultrasound Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1)
Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation across the tested population.
Measured: day 3 (+/-2)
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2)
Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation.
Measured: day 10 (+/-2)
Number of Participants With (Severe) Adverse Events
Number of AEs and SAEs occurring throughout the paradigm.
Measured: day 16 (+/-3)
Secondary outcomes (2)
Coma Recovery Scale Revised (CRS-R)
The Coma Recovery Scale Revised (CRS-R) is a standard clinical protocol specifically developed to assess a patient's level of consciousness, and does so by evaluating a patient's level of responsiveness to sensory stimulation, their ability to understand language, and to communicate. This procedure is typically administered at bedside. The protocol is divided into 6 sub-scales, each assessing a different area (e.g., visual function, auditory function, communication, arousal), and the final score is calculating by adding all sub-scales.The total score of this scale goes from its minimum, 0, which implied a state of coma, to 23, which implies emergence from a Minimally Conscious State (i.e., eMCS). Higher values thus map onto better outcomes.
Measured: Change in maximum CRS-R score in the 3 measurements following LIFUP (day of, day after, 1 week after) compared to the maximum CRS-R score in the 3 measurements prior to LIFUP (1 week before, day before, day of).
Glasgow Outcome Scale-Extended (GOS-E)
The Glasgow Outcome Scale extended (GOS-E) is a global scale that classifies functional outcome in brain injury patients. Specifically, the scale, which ranges from a minimum total score of 1 (i.e., Dead) to a maximum total score of 8 (Upper Good Recovery), classifies patient status into one of eight categories: Dead (score: 1), Vegetative State (score: 2), Lower Severe Disability (score: 3), Upper Severe Disability (score: 4), Lower Moderate Disability (score: 5), Upper Moderate Disability (score: 6), Lower Good Recovery (score: 7), or Upper Good Recovery (score: 8). Higher scores thus represent better outcomes. The score is determined according to specific answers given in the instrument.
Measured: day 16 (+/-3) and day 180 (+/-15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study start10 Mar 2016
- Primary completion3 Nov 2020
- Study completion3 Nov 2020
Why it stopped: COVID-19 restrictions placed on the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Consciousness DisordersStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 15 acute DOC patients and 15 chronic DOC patients.
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- The Dana Foundation, Tiny Blue Dot Foundation
- Responsible party
- Principal investigator, Martin M Monti, University of California, Los Angeles
- Investigators
- Martin M Monti, Prof, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02522429
- Sponsor's protocol ID
- 441488-MM-58041
- Acronym
- LIFUP
- Status last verified
- Nov 2022
- First submitted
- 6 Aug 2015
- Last updated
- 28 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thalamic Low Intensity Focused Ultrasound Stimulation in Disorders of Consciousness Following Severe Brain Injury
- ClinicalTrials.gov ID
- NCT02522429
- Acronym / sponsor ID
- LIFUP / 441488-MM-58041
- Conditions
- Consciousness Disorders, Brain Injuries
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID-19 restrictions placed on the study.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- The Dana Foundation, Tiny Blue Dot Foundation
- Study start
- 10 Mar 2016 (actual)
- Primary completion
- 3 Nov 2020 (actual)
- Study completion
- 3 Nov 2020 (actual)
- First posted
- 13 Aug 2015 (estimated)
- Results
- Posted 28 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness. To date there exists no standard intervention for patients suffering from these devastating conditions. The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for those patients. In this study, LIFUP will be performed during two sessions. The proposed experiment will involve behavioral and paramedical measurements just before and after each of the two LIFUP sessions in a small sample of patients (up to 15 acute and 15 chronic patients) in order to evaluate the feasibility of a full scale clinical trial.
Detailed description
Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness (DOC). Typically developed after severe brain injury, this set of related conditions includes Coma, the Vegetative State (VS) and the Minimally Conscious State (MCS). In the past 20 years, an increasing amount of research has broken many conventions about these disorders, including the once widespread belief that these patients are entirely apallic - that is, lack any kind of "higher" activity. Since then, it has been shown that a lot of brain activity, including relatively high-level cognitive processes, can remain in DOC patients. Nonetheless, to date there exists no standard intervention for patients suffering from these devastating conditions. Developing interventions for this population is extremely important first and foremost for the well-being of patients, who - today - remain completely dependent on assisted care, are often unable to participate in rehabilitative programs because of their lack of behavioral responsiveness, and thus find themselves prisoners of a condition characterized by uncertainty at the medical, legal and ethical decision-making levels. In addition, these conditions, which can last indefinitely, also place great emotional and monetary strain on families, large burdens on care-takers - often leading to increased rates of burn-out - and large financial stress on medical structures and public finances due to the large costs imposed by prolonged intensive care.
The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for patients with severe brain injury.
LIFUP will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session) in a small sample of patients (up to 15 acute and 15 chronic DOC patients) in order to evaluate the feasibility of a full scale clinical trial.
The duration of participation in the study will be a year. In terms of impact, we think this project would have a number of immediate consequences. (i) A successful pilot study and any indication that this approach might have the hypothesized effect would place us in a unique position to initiate a fully-fledged double-blind clinical trial in a large cohort of patients.
(ii) From a purely scientific point of view, by virtue of testing what is today the most prominent physiological hypothesis concerning loss and recovery of consciousness after severe brain injury, this project has a direct repercussion on our understanding of the mechanisms underlying these conditions. (iii) From a clinical and patient management point of view the present project is the first necessary step towards opening a completely new avenue for care-taking in patients suffering from this devastating condition for which there is no intervention. In particular, if this project were successful in the long run (e.g., after a double-blind full clinical trial), it could make widely available a non-invasive protocol which could substitute the currently highly invasive (and therefore not widely available, and high risk) only intervention available.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 15 acute DOC patients and 15 chronic DOC patients.
| Arm | Type | Receives |
|---|---|---|
| Low Intensity Focused Ultrasound Device | Experimental | Device: Low Intensity Focused Ultrasound Device15 acute DOC patients, 15 chronic DOC patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Acute patients
- < 6 weeks since injury
- a Glasgow Coma Score < 9 (at the time of injury)
- an abnormal CT
- prolonged loss of consciousness (>24h)
Key exclusion criteria (3 listed)
- deep sedation
- history of neurological illness prior to injury
- inability to safely enter the MR environment (e.g., ferromagnetic non MR safe implants)
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 |
|---|---|---|
| Low Intensity Focused Ultrasound DeviceAlso: BX Pulsar 1001, BX Pulsar 1002Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI and EEG) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session). | Device | Low Intensity Focused Ultrasound Device |
Primary outcome
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1)
Time frame: day 3 (+/-2)
Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation across the tested population.
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2)
Time frame: day 10 (+/-2)
Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation.
Number of Participants With (Severe) Adverse Events
Time frame: day 16 (+/-3)
Number of AEs and SAEs occurring throughout the paradigm.
2 secondary outcomes
Coma Recovery Scale Revised (CRS-R)
Time frame: Change in maximum CRS-R score in the 3 measurements following LIFUP (day of, day after, 1 week after) compared to the maximum CRS-R score in the 3 measurements prior to LIFUP (1 week before, day before, day of).
Glasgow Outcome Scale-Extended (GOS-E)
Time frame: day 16 (+/-3) and day 180 (+/-15)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Martin M Monti, Prof 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 Low Intensity Focused Ultrasound Device in people with Consciousness Disorders and Brain Injuries, run by University of California, Los Angeles 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 9 inclusion and 3 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: stopped early, as of the sponsor's last update on 28 Dec 2022. 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?
Yes. Results are posted in the registry (first posted 28 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1) (time frame: day 3 (+/-2)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2022.