Anoxia, Brain, Coma; Prolonged, CVA (Cerebrovascular Accident), Disorder of Consciousness, Minimally Conscious State, Minimally Conscious State Minus, Minimally Conscious State Plus, Thalamic Infarction, Traumatic Brain Injury, Vegetative State
Conditions
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.
Interventions
DEVICEBX 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.
Sponsors
University of California, Los Angeles
Tiny Blue Dot Foundation
Casa Colina Hospital and Centers for Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coma Recovery Scale-Revised | 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 | 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 | This will be conducted on Day 4. | Assess change in local standard uptake value (SUV) and global SUV. |
| Polysomnography | This will be conducted Day 1-10 of the study. | Change in nightly average density of sleep-spindles and sleep structure. |
Countries
United States
Outcome results
None listed