Advanced MRI Applications for Mild Traumatic Brain Injury (TBI)

• ClinicalTrials.gov Identifier: NCT02070588
• Recruitment Status: Terminated
• First Posted: February 25, 2014
• Results First Posted: July 21, 2017
• Last Update Posted: July 21, 2017
• Sponsor: GE Healthcare
• Information provided by (Responsible Party): GE Healthcare

Study Description

Brief Summary:

This feasibility study is being conducted to determine potential associations between a broad range of clinical neurological symptoms and magnetic resonance images (MRI), data, and clinical findings involved in mild traumatic brain injury (mTBI).

These associations will be examined over the acute and sub-acute period (approximately 3 months) following injury to provide information useful for optimization of MR pulse sequences for mTBI applications.

Correlations exist over the sub-acute period in clinical neurological and MR data (images, image reads, and RAW data), which may indicate temporal evolution patterns. The intent of this study is to broadly generate potential biomarkers of temporal evolution of mTBI detectable in MR images and data ("MR mTBI biomarkers").

Condition or disease	Intervention/treatment	Phase
Mild Traumatic Brain Injury; Traumatic Brain Injury	Device: MRI	Not Applicable

Detailed Description:

This hypothesis-generating feasibility study is being conducted to determine potential associations between a broad range of clinical neurological symptoms and MR images, data, and clinical findings involved in mild traumatic brain injury (mTBI). These associations will be examined over the acute and sub-acute period (approximately 3 months) following injury to provide information useful for optimization of MR pulse sequences for mTBI applications.

The intent of this study is to broadly generate a range of potential mTBI biomarkers detectable using investigational MR pulse sequence technologies. Feasibility data attained in this study may be used for engineering program decision-making and in support of future scientific assessment, engineering development, published research databases or registries mTBI data and images, and other purposes determined by the Sponsor. The results of this study are not intended for use in regulatory submissions.

Subjects will be examined on commercially available MR scanners using investigational or standard of care MR coils and a series of investigational MR Pulse Sequence sets (Application Packs). Each Application Pack will consist of a predetermined sequence of investigational pulse sequences (IPSs) optimized by GE Healthcare (GEHC) for mTBI. IPSs will be administered in a predetermined order as part of each Application Pack.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 112 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Advanced MRI Applications for Mild Traumatic Brain Injury
• Study Start Date: February 2014
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Experimental: Diagnostic mTBI; MRI Diagnostic of subjects with mild Tramatic Brain Injury (mTBI)	Device: MRI; MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects; Other Names: Discovery MR750 & Discovery MR750w scanners; Investigation software; Comericial nuerological coil (3T Advanced Neurological (Brain) Array MR Coil)
Placebo Comparator: Experimental: Diagnostic Non mTBI; MRI Diagnostic of Non injured subjects that are closely matched to mTBI	Device: MRI; MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects; Other Names: Discovery MR750 & Discovery MR750w scanners; Investigation software; Comericial nuerological coil (3T Advanced Neurological (Brain) Array MR Coil)

Outcome Measures

Primary Outcome Measures :

1. mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software [ Time Frame: Per-patient 1 to 3 months, until dataset completion 1 yr ]
   To determine associations between clinical neurological data, MR images, quantitative data from novel software post-processing (sponsor developed software including volumetry, Resting State [RS] functional magnetic resonance imaging [fMRI], kurtosis).

Secondary Outcome Measures :

1. Subject Demographics [ Time Frame: Per-patient 1 to 3 months, until dataset completion 1 yr ]
   To comprehensively collect subject information (i.e. baseline health data, demographics, socioeconomics, injury presentation, post-injury status, and injury type, place, and cause) for mTBI subjects in context of MRI data.
2. Operator Set MRI Parameters [ Time Frame: Per-patient 1 to 3 months, until dataset completion 1 yr ]
   To record operator-adjusted parameters of the novel software on the MRI system

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Segment 1: Inclusion Criteria for mTBI subjects

Subjects included in the main part of this study (Segment 1) will:

1. Be aged ≥15 and ≤50 years old at the time of enrollment;

2. Be diagnosed with mTBI according to the standard diagnostic procedures at the investigational site in a timeframe that meets enrollment criteria for enrollment in one of the first two intervals of the study, as follows:

   1. Meets criteria for enrollment in Encounter 1 (within 72 hours) OR
   2. Meets criteria for enrollment in Encounter 2 (within 8±2 days)
3. Be capable of sufficiently clear communication to allow the subject to provide written informed consent, or assent with parental or guardian consent for minors as described in Section 6.3 - Protection of Vulnerable Subjects, for participation in all parts of the study.

Segment 1: Exclusion Criteria for mTBI subjects

Subjects will be excluded that have:

1. Loss of consciousness (LOC) ≥15 minutes;
2. Posttraumatic amnesia lasting ≥24 hr following a recent TBI event;
3. Diagnosis of moderate to severe TBI or GCS <13;
4. Structural brain injury indicated by previous neuroimaging findings;
5. Previous history of moderate to severe TBI;
6. Any previous history of mild TBI within the past 12 months;
7. Previously diagnosed brain white matter disease;
8. History of seizures within the past 10 years;
9. History of self-reported illicit drug abuse (except marijuana) in past 10 years;
10. History of alcohol abuse or dependence (per DSM-IV-TR Diagnostic Criteria);
11. Current primary Axis I or II psychiatric disorders, except for disorders classified as minor and not expected to impact study conduct or integrity (as detailed in Appendix D - Screening for Exclusion based on Axis I or II Disorders):
12. History of brain mass
13. History of neurosurgery
14. History of stroke
15. History of dementia
16. Known cognitive dysfunction
17. Known structural brain disease or malformation
18. Current anti-psychotic or antiepileptic medication usage
19. That are unable or unwilling to complete study procedures accurately or have any conflict of interest that could affect study results, in the opinion of the investigator;

20. Contraindications to MRI scanning, including:

    1. Current or suspected pregnancy per site clinical practice;
    2. Other conditions that may constitute a hazard to the subject during study participation, determined by the investigator;
    3. Inability to comply with any part of the site's MR safety policy.

Inclusion Criteria for Non-TBI subjects (Segment 2)

All included subjects will:

1. Aged ≥15 and ≤50 years old at the time of enrollment;

2. Be well matched to one or more mTBI patients in Segment 1, in the opinion of the Principal Investigator, with regards to:

   1. Age,
   2. Gender,
   3. Sociodemographic characteristics, and
   4. Handedness.
3. Be capable of sufficiently clear communication to allow the subject to provide written informed consent, or assent with parental or guardian consent for minors as described in Section 6.3 - Protection of Vulnerable Subjects, for participation in all parts of the study.

Exclusion Criteria for Non-TBI subjects (Segment 2)

Subjects will be excluded that:

1. Are currently pregnant based on subject self-report of pregnancy status;
2. Are currently enrolled in another Segment of this study;
3. Require medical care that would be adversely affected or delayed by participating, in the opinion of a physician investigator;
4. Prior diagnosis of mild TBI within the past 12 months;
5. Have structural brain injury indicated by previous neuroimaging findings;
6. Previous history of moderate to severe TBI within the past 10 years;
7. Previously diagnosed brain white matter disease;
8. History of seizures within the past 10 years;
9. History of illicit drug abuse (except marijuana) within the past 10 years
10. History of alcohol abuse or dependence (per DSM-IV-TR Diagnostic Criteria);
11. Current primary Axis I or II psychiatric disorders, except for disorders classified as minor and not expected to impact study conduct or integrity (as detailed in Appendix D - Screening for Exclusion based on Axis I or II Disorders):
12. History of brain mass;
13. History of neurosurgery;
14. History of stroke;
15. History of dementia;
16. Known cognitive dysfunction;

Contacts and Locations

Locations

United States, New York

Hospital for Special Surgery

New York, New York, United States, 08540

Sponsors and Collaborators

GE Healthcare

Investigators

• Principal Investigator: Teena Shetty, MD; Hospital for Special Surgery, New York

More Information

• Responsible Party: GE Healthcare
• ClinicalTrials.gov Identifier: NCT02070588
• Other Study ID Numbers: 114-2013-GES-0017
• First Posted: February 25, 2014
• Results First Posted: July 21, 2017
• Last Update Posted: July 21, 2017
• Last Verified: June 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by GE Healthcare:

TBI; mTBI; MR; MRI; Pulse Sequences; NFL

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating