Resting State fMRI in Disorders of Consciousness

NCT05463029 | Terminated

• 1 other identifier: 851120
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Disorders of consciousness (DoC) remain a major clinical challenge in which high rates of misdiagnosis and difficult prognostication stem from limitations in the ability to access the disordered physiological processes mechanisms of coma in real world clinical settings. There is a great need to develop, validate, and translate to clinical use reliable diagnostics to detect brain recovery potential not evident on neurobehavioral assessment. While resting state fMRI (rs-fMRI) has demonstrated potential to improve the diagnostic evaluation of DoC by detecting features of consciousness that are occult at bedside evaluation, this technology has yet to achieve widespread clinical utility. The investigators propose that recent advancements in rs-fMRI capabilities can be combined with streamlined analysis and interpretation approaches to overcome persistent intensive care unit to perform rs-fMRI in patients with prolonged impaired consciousness due to several causes including TBI, cardiac arrest, stroke, seizures, and severe CNS infection. The investigators will determine the optimal methods of data acquisition, analysis and interpretation for predicting recovery of consciousness in these patients. Our expectations are that this approach will produce highly reliable functional connectomic characterization of individual DoC patients, thereby allowing for more accurate outcome prediction. The investigators will additionally investigate the utility of a novel, simplified radiological approach to rs-fMRI data interpretation in comparison to computationally intensive connectomic approaches. This exploratory/developmental project is expected to provide critical data needed to design and appropriately power future R01 studies validating the efficacy of fMRI-based network integrity in the clinical evaluation of DoC.

Conditions

Disorders of Consciousness

Outcome Measures

Primary Outcomes (1)

• Interclass correlation coefficient of functional-connectivity measures

  The interclass correlation coefficient (ICC) is used to assess the reliability of functional connectivity measures.

  Assessed at the time of the scan (for the coma patients within 1 week of DoC onset).

Secondary Outcomes (3)

• Glasgow Coma Scale (GCS)

  The GCS is assessed at the time of the scan as well as at 10 days post-MRI.

• Physical therapy-based functional status examination scores

  Physical therapy-based functional status exam scores are assessed at 10 days post-MRI

• Weighted Kappa of radiological connectivity ratings

  Assessed at the time of the scan (for the coma patients within 1 week of DoC onset).

Study Arms (2)

Healthy Controls

Healthy control participants will be recruited from the general population through the use of flyers and other means of advertising.

Affected Patients

Research staff locate eligible patients in the hospital through real-time medical record review at the time of initial presentation to the NICU or request for neurology consultation for patients in the MICU or CCU. Once potential patients have been identified, research staff will approach their Legally Authorized Representative to introduce the study and initiate the informed consent process, if appropriate.

Eligibility Criteria

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

Study Population

Patients with prolonged impaired consciousness (greater than 48 hours) due to several causes including TBI, cardiac arrest, stroke, seizures, and severe CNS infection. Demographically-similar healthy control subjects

You may qualify if:

• Adults 18 years of age or older diagnosed with acute DoC (defined by a Glasgow Coma Scale (GCS) motor score less than 6 and GCS verbal score less than 3 persisting at least 48 hours) due to trauma, cardiac arrest, stroke, seizure, or severe CNS infection.

You may not qualify if:

• Children under 18
• Contraindications to MRI (medical instability, non-MRI compatible implanted devices, retained metallic foreign bodies, claustrophobia)
• Presence of artifact-producing intracranial devices (aneurysm clips/coils, ventricular drains, craniectomy mesh, etc.)
• Large space-occupying lesions (50 mL) or substantial mass effect (herniation, 5mm midline shift) on preceding brain imaging
• Imminently life-threatening co-morbid conditions
• History of premorbid disabling neurological or psychiatric disease
• Current substance abuse or remote substance abuse with permanent organic sequelae
• Pregnancy

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Consciousness Disorders

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jeffrey Ware, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 18, 2022
• Study Start: August 1, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

US (1)