Thalamic Low Intensity Focused Ultrasound in Brain Injury (LIFUP)

• ClinicalTrials.gov Identifier: NCT02522429
• Recruitment Status: Recruiting
• First Posted: August 13, 2015
• Last Update Posted: August 7, 2020
• Sponsor: University of California, Los Angeles
• Collaborators: The Dana Foundation; Tiny Blue Dot Foundation
• Information provided by (Responsible Party): Martin M Monti, University of California, Los Angeles

Study Description

Brief Summary:

Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness. To date there exists no standard intervention for patients suffering from these devastating conditions. The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for those patients. In this study, LIFUP will be performed during two sessions. The proposed experiment will involve behavioral and paramedical measurements just before and after each of the two LIFUP sessions in a small sample of patients (up to 15 acute and 15 chronic patients) in order to evaluate the feasibility of a full scale clinical trial.

Condition or disease	Intervention/treatment	Phase
Consciousness Disorders; Brain Injuries	Device: Low Intensity Focused Ultrasound Device	Not Applicable

Detailed Description:

Few neurological conditions are as scientifically mysterious and clinically, legally, and ethically challenging as disorders of consciousness (DOC). Typically developed after severe brain injury, this set of related conditions includes Coma, the Vegetative State (VS) and the Minimally Conscious State (MCS). In the past 20 years, an increasing amount of research has broken many conventions about these disorders, including the once widespread belief that these patients are entirely apallic - that is, lack any kind of "higher" activity. Since then, it has been shown that a lot of brain activity, including relatively high-level cognitive processes, can remain in DOC patients. Nonetheless, to date there exists no standard intervention for patients suffering from these devastating conditions. Developing interventions for this population is extremely important first and foremost for the well-being of patients, who - today - remain completely dependent on assisted care, are often unable to participate in rehabilitative programs because of their lack of behavioral responsiveness, and thus find themselves prisoners of a condition characterized by uncertainty at the medical, legal and ethical decision-making levels. In addition, these conditions, which can last indefinitely, also place great emotional and monetary strain on families, large burdens on care-takers - often leading to increased rates of burn-out - and large financial stress on medical structures and public finances due to the large costs imposed by prolonged intensive care.

The present project is aimed at evaluating the potential of non-invasive Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) as a neurorestorative stimulation for patients with severe brain injury.

LIFUP will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI and EEG) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session) in a small sample of patients (up to 15 acute and 15 chronic DOC patients) in order to evaluate the feasibility of a full scale clinical trial.

Outcome measures (i.e., GOSE and CRS-R) will be administered at discharge and follow-up. The duration of participation in the study will be a year.

In terms of impact, we think this project would have a number of immediate consequences. (i) A successful pilot study and any indication that this approach might have the hypothesized effect would place us in a unique position to initiate a fully-fledged double-blind clinical trial in a large cohort of patients.

(ii) From a purely scientific point of view, by virtue of testing what is today the most prominent physiological hypothesis concerning loss and recovery of consciousness after severe brain injury, this project has a direct repercussion on our understanding of the mechanisms underlying these conditions. (iii) From a clinical and patient management point of view the present project is the first necessary step towards opening a completely new avenue for care-taking in patients suffering from this devastating condition for which there is no intervention. In particular, if this project were successful in the long run (e.g., after a double-blind full clinical trial), it could make widely available a non-invasive protocol which could substitute the currently highly invasive (and therefore not widely available, and high risk) only intervention available.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 15 acute DOC patients and 15 chronic DOC patients.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Thalamic Low Intensity Focused Ultrasound Stimulation in Disorders of Consciousness Following Severe Brain Injury
• Actual Study Start Date: March 10, 2016
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Low Intensity Focused Ultrasound Device; 15 acute DOC patients, 15 chronic DOC patients

Device: Low Intensity Focused Ultrasound Device; Low Intensity Focused Ultrasound Pulsation (LIFUP) of thalamus (a key area for the consciousness network) will be performed during two sessions (one occurring after deep sedation is stopped and the second one occurring just before discharge). The proposed experiment will involve behavioral (i.e., CRS-R) and paramedical (i.e., MRI/fMRI and EEG) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session).; Other Names: BX Pulsar 1001; BX Pulsar 1002

Outcome Measures

Primary Outcome Measures :

1. Brain structure as assessed by Magnetic Resonance Imaging (MRI) (Session 1) [ Time Frame: 1 week post-LIFUP exposure #1 ]
   MRI is a widely used method to assess body tissues, including the brain, in a non-invasive manner. In the context of this study, MRI will be used to assess brain structure (expected total duration 10 minutes).
2. Brain function as assessed by functional Magnetic Resonance Imaging (fMRI) (Session 1) [ Time Frame: 1 week post-LIFUP exposure #1 ]
   fMRI is a neuroimaging procedure using MRI technology that measures brain function. We will assess brain activity in response to auditory stimulation (expected total duration of 20 minutes).
3. Brain structure as assessed by Magnetic Resonance Imaging (MRI) (Session 2) [ Time Frame: 1 week post-LIFUP exposure #2 ]
   MRI is a widely used method to assess body tissues, including the brain, in a non-invasive manner. In the context of this study, MRI will be used to assess brain structure (expected total duration 10 minutes).
4. Brain function as assessed by functional Magnetic Resonance Imaging (fMRI) (Session 2) [ Time Frame: 1 week post-LIFUP exposure #2 ]
   fMRI is a neuroimaging procedure using MRI technology that measures brain function. We will assess brain activity in response to auditory stimulation (expected total duration of 20 minutes).
5. (Severe) Adverse Event Number [ Time Frame: Typically 14 days post beginning of the protocol ]
   Number of AEs and SAEs occurring throughout the 2-week paradigm.

Secondary Outcome Measures :

1. Coma Recovery Scale Revised (CRS-R) [ Time Frame: 1 week post-LIFUP exposure #1 and 1 week post-LIFUP exposure #2 ]
   The CRS-R is a standard clinical protocol used to assess a patient's level of consciousness. This test allows us to assess the level of response to sensory stimulation, ability to understand language and to communicate. This procedure is typically administered at bedside. This testing should take 25 minutes, and will consist of simple requests (such as "close your eyes" and "open your mouth").
2. Electroencephalography (EEG) [ Time Frame: 1 week post-LIFUP exposure #1 and 1 week post-LIFUP exposure #2 ]
   EEG is a widely employed technique that measures electrical brain activity. This procedure (expected duration: 10 minutes + set-up time, up to 20 minutes) will allow us to measure electrical brain activity at rest. This procedure is entirely non-invasive.
3. Glasgow Outcome Scale-Extended (GOS-E) [ Time Frame: typically at 14 days post-enrollment and at follow-up (6 months post-enrollment) ]
   The GOS-E is a standard clinical scale used to classify outcome in survivors with brain injuries. This brief assessment takes less than 10 minutes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Acute patients

• < 6 weeks since injury
• a Glasgow Coma Score < 9 (at the time of injury)
• an abnormal CT
• prolonged loss of consciousness (>24h)
• behavioral profile consistent with a VS or MCS as assessed with the Coma Recovery Scale Revised.

Chronic patients:

• > 3 months post injury for non-traumatic injuries, >12 months post-injury for traumatic injuries
• behavioral profile consistent with a VS or MCS as assessed with the Coma Recovery Scale Revised.

Exclusion Criteria (all patients):

• deep sedation
• history of neurological illness prior to injury
• inability to safely enter the MR environment (e.g., ferromagnetic non MR safe implants)

Contacts and Locations

Contacts

Contact: Martin M Monti, Prof; 310-825-8546; monti@ucla.edu

Contact: Caroline Schnakers, PhD; cschnakers@ucla.edu

Locations

United States, California

University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90095-1563

Contact: Caroline Schnakers, PhD 310-825-8546 cschnakers@ucla.edu

Principal Investigator: Martin M Monti, PhD

Sponsors and Collaborators

University of California, Los Angeles

The Dana Foundation

Tiny Blue Dot Foundation

Investigators

• Principal Investigator: Martin M Monti, Prof; University of California, Los Angeles

More Information

• Responsible Party: Martin M Monti, Assistant Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT02522429
• Other Study ID Numbers: 441488-MM-58041
• First Posted: August 13, 2015
• Last Update Posted: August 7, 2020
• Last Verified: August 2020

Additional relevant MeSH terms:

Brain Injuries; Consciousness Disorders; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Neurobehavioral Manifestations; Neurologic Manifestations; Neurocognitive Disorders; Mental Disorders