The Use of LIFUP in Chronic Disorders of Consciousness

Casa Colina Hospital and Centers for Healthcare16 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Disorder of Consciousness

Interventions

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Coma Recovery Scale-Revised

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.

Electroencephalography

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.

Positron Emission Tomography

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

Time frame: This will be conducted on Day 4.

Polysomnography

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

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