The Use of LIFUP in Chronic Disorders of Consciousness

NCT04921683 | Completed DMC FDA Device

• 1 other identifier: IRB#21-000091
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Disorder of Consciousness; Vegetative State; Minimally Conscious State; Minimally Conscious State Plus; Minimally Conscious State Minus; Traumatic Brain Injury; CVA (Cerebrovascular Accident); Anoxia, Brain; Thalamic Infarction; Coma; Prolonged

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

• Positron Emission Tomography

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

  This will be conducted on Day 4.

• Polysomnography

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

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

Study Arms (1)

Treatment LIFUP

EXPERIMENTAL

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 to minimize bone absorption and refraction. Accurate aiming will be ensured using the Brain Sight neuronavigation device, customized for tracking our LIFUP transducer. Following LIFUP, the patient will undergo a second EEG session, except for the EEG cap being fit to the patient's head prior to the LIFUP session so that, as soon as LIFUP administration is complete, the EEG paradigm can be promptly administered. The patient will then be allowed to rest (\~1h).The patient will then be administered a second dose of tracer in order to undergo a second PET measurement. Finally, at the end-of-day, the clinical coordinator will collect an Adverse Event Questionnaire and will fit the PSG device for night monitoring.

Device: BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation

Interventions

BX Pulsar 1002 (LIFUP) Low intensity Focused Ultrasound Pulsation DEVICE

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.

Treatment LIFUP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of VS or MCS based on the CRS-R .
• Chronic status:
• months post-injury for non-traumatic etiologies
• months post-injury for traumatic etiology
• years of age or older.
• 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.

You may not qualify if:

• History of neurological disorder (other than the brain injury).
• Unsuitability to undergo Magnetic Resonance (MR) assessment (e.g., non-MR compatible implants).
• 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).
• Manifest continuous spontaneous movement (which would prevent imaging)
• Participation in another concurrent clinical trial.
• 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.
• Dependence on ventilator.

Sponsors & Collaborators

• Casa Colina Hospital and Centers for Healthcare: lead
• University of California, Los Angeles: collaborator
• Tiny Blue Dot Foundation: collaborator

Study Sites (1)

Casa Colina Hospital

Pomona, California, 91709, United States

Location

Related 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.

  PMID: 10869046 RESULT

• 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. Epub 2016 Jul 22. No abstract available.

  PMID: 27567470 RESULT

• 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.

  PMID: 22224835 RESULT

• 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.brs.2019.07.024. Epub 2019 Jul 31.

  PMID: 31401074 RESULT

• 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.

  PMID: 28901969 RESULT

• 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.

  PMID: 21876461 RESULT

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State; Brain Injuries, Traumatic; Stroke; Hypoxia, Brain; Coma

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory

Study Officials

• Caroline Schnakers, PhD

  Casa Colina Hospital and Centers for Healthcare

  PRINCIPAL INVESTIGATOR

• Martin Monti, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Director of Research

Model Details: 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.

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 10, 2021
• Study Start: June 21, 2021
• Primary Completion: March 1, 2023
• Study Completion: April 14, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)