Thalamic Low Intensity Focused Ultrasound in Brain Injury

NCT02522429 | Terminated Results DMC

• 1 other identifier: 441488-MM-58041
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Consciousness Disorders; Brain Injuries

Outcome Measures

Primary Outcomes (3)

• Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP Across the Whole Group (Session 1)

  Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation across the tested population.

  day 3 (+/-2)

• Number of Voxels in Which the Functional Magnetic Resonance Imaging (fMRI) Signal is Significantly Associated to LIFUP (Session 2)

  Number of voxels found to have a functional MRI signal (measured with a Blood Oxygenation Level Dependent sequence) significantly associated with the onset/offset of the LIFUP stimulation.

  day 10 (+/-2)

• Number of Participants With (Severe) Adverse Events

  Number of AEs and SAEs occurring throughout the paradigm.

  day 16 (+/-3)

Secondary Outcomes (2)

• Coma Recovery Scale Revised (CRS-R)

  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).

• Glasgow Outcome Scale-Extended (GOS-E)

  day 16 (+/-3) and day 180 (+/-15)

Study Arms (1)

Low Intensity Focused Ultrasound Device

EXPERIMENTAL

15 acute DOC patients, 15 chronic DOC patients

Device: Low Intensity Focused Ultrasound Device

Interventions

Low Intensity Focused Ultrasound Device 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).

Also known as: BX Pulsar 1001, BX Pulsar 1002

Low Intensity Focused Ultrasound Device

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• The Dana Foundation: collaborator
• Tiny Blue Dot Foundation: collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095-1563, United States

Location

MeSH Terms

Conditions

Consciousness Disorders; Brain Injuries

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Limitations and Caveats

1. Early termination due to COVID-19 imposed restrictions prevented acquisition of intended sample and follow-up data for a majority of patients. 2. Length of the protocol on each exposure session prevented acquisition of the originally planned structural MRI (for Primary outcomes #1, #3) and the EEG data before/after exposure (for Secondary outcome #2). 3. Loss of majority of Acute patients to follow-up prevents meaningful group analysis for Primary outcome #4 in the Acute cohort.

Results Point of Contact

• Title: Principal Investigator
• Organization: UCLA

monti@ucla.edu

3108258546

Study Officials

• Martin M Monti, Prof

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 15 acute DOC patients and 15 chronic DOC patients.

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 13, 2015
• Study Start: March 10, 2016
• Primary Completion: November 3, 2020
• Study Completion: November 3, 2020
• Last Updated: December 28, 2022
• Results First Posted: December 28, 2022

Record last verified: 2022-11

Locations

US (1)