Prognostication of Recovery in Early Disorders of Consciousness Study

NCT07074678 | Enrolling By Invitation

• 2 other identifiers: 8523811K23NS136745-01A1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine the extent to which neuroimaging metrics (e.g., functional MRI) are associated with the current level of consciousness, and future consciousness recovery, in patients with disorders of consciousness resulting from acute brain injury. The main questions this study aims to answer are: How do functional MRI findings (e.g., covert consciousness and network connectivity) associate with current level of consciousness? How do functional MRI findings (e.g., covert consciousness and network connectivity) associate with future recovery of consciousness? How does noxious stimulation affect the detection of covert consciousness and functional brain network connectivity?

Conditions

Disorder of Consciousness; Comatose; Coma; Prolonged; Vegetative State; Minimally Conscious State

Outcome Measures

Primary Outcomes (4)

• Detection of technologic covert consciousness

  Brain activity during the delivery of commands, as compared to brain activity during rest, will be measured during the functional MRI scan. Brain activity that is significantly more associated with commands and that occurs in the premotor cortex or supplementary motor area will be interpreted as evidence of technologic covert consciousness.

  Baseline, during hospitalization (estimated approximately 1 month from brain injury)

• Functional network connectivity

  Functional connectivity of brain networks will be measured during a resting state functional MRI sequence without noxious stimulation. Another sequence may be obtained during noxious stimulation.

  Baseline, during hospitalization (estimated approximately 1 month from brain injury)

• Detection of behavioral covert consciousness

  The Coma Recovery Scale - Revised (CRS-R) will be used to assess the presence of behavioral covert consciousness, defined as the minimally conscious state minus (non-language based, but purposeful, behaviors), or the minimally conscious state plus (command-following, intelligible verbalization, and intentional communication). Higher scores (maximum 23) reflect higher levels of consciousness than lower scores (minimum 0).

  Baseline, during hospitalization (estimated approximately 1 month from brain injury), within 24 hours of the functional MRI

• Overt consciousness recovery based on Disability Rating Scale

  Overt consciousness, defined as command-following as measured with the Disability Rating Scale, will be evaluated at hospital discharge, and 3 and 6 months afterwards.

  Through study completion: At hospital discharge (estimated approximately 1 month from brain injury), 3 months after hospital discharge, and 6 months after hospital discharge

Study Arms (1)

Single arm

EXPERIMENTAL

Patients and healthy controls will undergo functional MRI, which may include auditory and noxious stimulation.

Diagnostic Test: Functional MRI (fMRI)

Interventions

Functional MRI (fMRI) DIAGNOSTIC_TEST

Research MRI, which will include both structural and functional sequences, will either be collected independently, or in conjunction with clinically-indicated sequences. Functional MRI captures the blood oxygen level dependent (BOLD) signal that reflects brain activity. A subset of the PREDICT study fMRI will include sequences with auditory and/or noxious stimulation. Noxious stimulation will be delivered with an MRI-compatible device that delivers intermittent nailbed pressure under computerized control. Additionally, the BOLD signal will be captured at rest to investigate functional neural networks.

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute brain injury (including, but not limited to ischemic stroke, intracranial hemorrhage, anoxic brain injury, traumatic brain injury, or encephalitis)
• Inability to follow commands due to a disorder of consciousness (comatose, vegetative, or minimally conscious state) caused by the underlying brain injury
• Age 18 or greater
• Enrolled within 28 days of brain injury

You may not qualify if:

• Imminent death (as indicated, for example, by planned transition to palliative measures, brain death testing, or severe medical instability)
• MRI contraindications would exclude patients from imaging component of study
• For healthy controls:
• MRI contraindications
• History of brain injury to neurological disease
• History of diabetes, high blood pressure, kidney disease

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Consciousness Disorders; Coma; Persistent Vegetative State

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Unconsciousness; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• David J Fischer, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: July 20, 2025
• Study Start: March 8, 2023
• Primary Completion (Estimated): March 8, 2028
• Study Completion (Estimated): March 8, 2029
• Last Updated: July 20, 2025

Record last verified: 2025-07

Locations

US (1)