Clinical trial NCT04921683: The Use of LIFUP in Chronic Disorders of Consciousness
Official title: Biomarkers of Thalamic LIFUP in Chronic Disorders of Consciousness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Casa Colina Hospital and Centers for Healthcare
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: Tiny Blue Dot Foundation
First posted: 2021-06-10
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Coma Recovery Scale-Revised
timeFrame: 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.
measure: Electroencephalography
timeFrame: The EEG will be conducted at Day 3, 4, 7 and 10 of the study.
measure: Positron Emission Tomography
timeFrame: This will be conducted on Day 4.
measure: Polysomnography
timeFrame: This will be conducted Day 1-10 of the study.
Secondary outcomes:
Other outcomes:
Locations:
city: Pomona
country: United States
facility: Casa Colina Hospital
state: California
Study officials:
affiliation: Casa Colina Hospital and Centers for Healthcare
name: Caroline Schnakers, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Martin Monti, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. Epub 2016 Jul 22. No abstract available.
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.
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.brs.2019.07.024. Epub 2019 Jul 31.
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.
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.