The Use of LIFUP in Chronic Disorders of Consciousness

Traumatic Brain Injury Clinical Trial

Official title:

Biomarkers of Thalamic LIFUP in Chronic Disorders of Consciousness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04921683
• Other study ID #: IRB#21-000091
• Status: Completed
• Phase: N/A
• Start date: June 21, 2021
• Est. completion date: April 14, 2023

Study information

• Verified date: May 2023
• Source: Casa Colina Hospital and Centers for Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 14, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Chronic Disease
• Coma; Prolonged
• Consciousness Disorders
• CVA (Cerebrovascular Accident)
• Disorder of Consciousness
• Hypoxia, Brain
• Infarction
• Minimally Conscious State
• Persistent Vegetative State
• Stroke
• Thalamic Infarction
• Traumatic Brain Injury
• Vegetative State

Intervention

Device:
• BX 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.

Locations

Country	Name	City	State
United States	Casa Colina Hospital	Pomona	California

Sponsors (3)

Lead Sponsor	Collaborator
Casa Colina Hospital and Centers for Healthcare	Tiny Blue Dot INC., UCLA Department of Psychology

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

Monti 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. E — View Citation

Monti 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. — View Citation

Pasquinelli 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 — View Citation

Schnakers 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. — View Citation

Yoo 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coma Recovery Scale-Revised	Change in maximum total and subscale scores.	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.
Primary	Electroencephalography	Change in fast to slow frequency power spectrum density and in P3b amplitude.	The EEG will be conducted at Day 3, 4, 7 and 10 of the study.
Primary	Positron Emission Tomography	Assess change in local standard uptake value (SUV) and global SUV.	This will be conducted on Day 4.
Primary	Polysomnography	Change in nightly average density of sleep-spindles and sleep structure.	This will be conducted Day 1-10 of the study.