Trial Outcomes & Findings for Thalamic Low Intensity Focused Ultrasound in Brain Injury (NCT NCT02522429)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

23 participants

Primary outcome timeframe

day 3 (+/-2)

Results posted on

2022-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Low Intensity Focused Ultrasound Device 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Overall Study STARTED	23
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Intensity Focused Ultrasound Device 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Overall Study Lost to Follow-up	8
Overall Study Adverse Event	2
Overall Study Death	1
Overall Study Patient exceeded inclusion criteria after enrollment but prior to undergoing study procedures	1

Baseline Characteristics

Reporting separately Acute and Chronic patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Intensity Focused Ultrasound Device n=23 Participants 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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).
Age, Continuous Acute	31 years n=13 Participants • Reporting separately Acute and Chronic patients
Age, Continuous Chronic	35 years n=10 Participants • Reporting separately Acute and Chronic patients
Sex: Female, Male Acute · Female	2 Participants n=13 Participants • Reporting separately Acute and Chronic patients
Sex: Female, Male Acute · Male	11 Participants n=13 Participants • Reporting separately Acute and Chronic patients
Sex: Female, Male Chronic · Female	4 Participants n=10 Participants • Reporting separately Acute and Chronic patients
Sex: Female, Male Chronic · Male	6 Participants n=10 Participants • Reporting separately Acute and Chronic patients
Region of Enrollment United States	23 participants n=23 Participants
Time Post Injury Acute	23 Days STANDARD_DEVIATION 28.32 • n=13 Participants • Reporting separately Acute and Chronic patients
Time Post Injury Chronic	1076 Days STANDARD_DEVIATION 2029 • n=10 Participants • Reporting separately Acute and Chronic patients

PRIMARY outcome

Timeframe: day 3 (+/-2)

Population: Separating Acute and Chronic patients

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.

Outcome measures

Outcome measures
Measure	Low Intensity Focused Ultrasound Device n=228453 Voxels 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1) Acute	211 Number of significant voxels
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1) Chronic	0 Number of significant voxels

PRIMARY outcome

Timeframe: day 10 (+/-2)

Population: Separating Acute and Chronic (including only patients who underwent a second session)

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.

Outcome measures

Outcome measures
Measure	Low Intensity Focused Ultrasound Device n=228453 Voxels 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2) Acute	0 Number of significant voxels
Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2) Chronic	0 Number of significant voxels

PRIMARY outcome

Timeframe: day 16 (+/-3)

Number of AEs and SAEs occurring throughout the paradigm.

Outcome measures

Outcome measures
Measure	Low Intensity Focused Ultrasound Device n=23 Participants 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Number of Participants With (Severe) Adverse Events	3 participants

SECONDARY outcome

Timeframe: 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).

Population: Reporting separately Acute and Chronic patients; higher scores mean better outcome

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.

Outcome measures

Outcome measures
Measure	Low Intensity Focused Ultrasound Device n=21 Participants 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Coma Recovery Scale Revised (CRS-R) Acute	2.8 score on a scale Standard Deviation 3.6
Coma Recovery Scale Revised (CRS-R) Chronic	1.5 score on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: day 16 (+/-3) and day 180 (+/-15)

Population: Separating Acute (7/11 lost to 14 day follow up; 9/11 lost to 6-month follow-up \[including COVID19 restrictions\]) and Chronic groups (1/10 lost to 14 day follow-up; 3/10 lost to 6-month follow-up \[including COVID19 restrictions\])

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.

Outcome measures

Outcome measures
Measure	Low Intensity Focused Ultrasound Device n=13 Participants 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Glasgow Outcome Scale-Extended (GOS-E) Acute (14-day follow-up)	3 score on a scale (higher scores better) Interval 2.0 to 3.0
Glasgow Outcome Scale-Extended (GOS-E) Chronic (14-day follow-up)	3 score on a scale (higher scores better) Interval 2.0 to 3.0
Glasgow Outcome Scale-Extended (GOS-E) Acute (6-month follow-up)	3 score on a scale (higher scores better) Interval 3.0 to 3.0
Glasgow Outcome Scale-Extended (GOS-E) Chronic (6-month follow-up)	3 score on a scale (higher scores better) Interval 2.0 to 3.0

Adverse Events

Low Intensity Focused Ultrasound Device

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Low Intensity Focused Ultrasound Device n=23 participants at risk 15 acute DOC patients, 15 chronic DOC patients Low Intensity Focused Ultrasound Device: 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) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).
Respiratory, thoracic and mediastinal disorders Respiratory depression (prior to any intervention procedure)	4.3% 1/23 • Number of events 1 • 2 weeks

Other adverse events

Adverse event data not reported

Additional Information

Principal Investigator

UCLA

Phone: 3108258546

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place