Clinical trial NCT02522429: Thalamic Low Intensity Focused Ultrasound in Brain Injury
Official title: Thalamic Low Intensity Focused Ultrasound Stimulation in Disorders of Consciousness Following Severe Brain Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Consciousness Disorders
Brain Injuries
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: The Dana Foundation
name: Tiny Blue Dot Foundation
First posted: 2015-08-13
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 15 acute DOC patients and 15 chronic DOC patients.
Primary purpose: TREATMENT

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.

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) 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.

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.

Eligibility 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)

Primary outcomes:
measure: Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1)
timeFrame: day 3 (+/-2)
measure: Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2)
timeFrame: day 10 (+/-2)
measure: Number of Participants With (Severe) Adverse Events
timeFrame: day 16 (+/-3)
Secondary outcomes:
measure: Coma Recovery Scale Revised (CRS-R)
timeFrame: Change in maximum CRS-R score in the 3 measurements following LIFUP (day of, day after, 1 week after) compared to the maximum CRS-R score in the 3 measurements prior to LIFUP (1 week before, day before, day of).
measure: Glasgow Outcome Scale-Extended (GOS-E)
timeFrame: day 16 (+/-3) and day 180 (+/-15)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Martin M Monti, Prof
role: PRINCIPAL_INVESTIGATOR
References: