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Myelin Imaging in Concussed High School Football Players

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ClinicalTrials.gov Identifier: NCT03698747
Recruitment Status : Terminated (PI left organization)
First Posted : October 9, 2018
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Healthcare System

Tracking Information
First Submitted Date October 4, 2018
First Posted Date October 9, 2018
Last Update Posted Date September 25, 2020
Actual Study Start Date September 4, 2018
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 4, 2018)
Myelin Disruption on MRI brain scan [ Time Frame: 3 months ]
Determine whether mTBI in football players leads to increased, but disorganized, myelin compared to non-contact sports players.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: October 4, 2018)
  • APoE4 allele genetic mutation on blood test [ Time Frame: 3 months ]
    Explore whether a genetic mutation in the APoE4 allele predisposes football players to decreased or disorganized myelination after mTBI.
  • Neuropsychiatric concussion correlation [ Time Frame: 3 months ]
    Correlate any changes in myelination or of genetics with neuropsychiatric concussion assessment.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Myelin Imaging in Concussed High School Football Players
Official Title A Prospective Study of Myelin Imaging Changes in Concussed High School Football Players
Brief Summary Investigate myelin alterations in high school football players with mTBI
Detailed Description

The lack of highly sensitive clinical neuroimaging and neuropsychiatric markers of subtle changes due to mTBI makes it difficult to characterize injury severity and to predict outcomes. White matter tracts in the brain, both myelinated and non-myelinated, are susceptible to damage from impact-acceleration forces experienced during a TBI,5-7 and there is evidence that significant white matter injury and myelin loss occurs in mTBI. In addition, this damage may be chronic and can negatively affect neural processing speed and cognitive function. Traditional anatomical and function MRI imaging sequences include clinical sequences such as traditional T1 and T2 sequences, fluid-attenuated inversion recovery (FLAIR), three-dimensional (3D) magnetization-prepared rapid gradient echo (MP-RAGE), diffusion-weighted imaging (DWI) and gradient MRI. While a number of advanced imaging techniques, notably magnetization transfer, diffusion tensor and quantitative T1 and T2 imaging (MTI, DTI, qT1 and qT2, respectively), have been used previously to study white matter in neurosurgical diseases, these methods provide only indirect, non-specific information related to myelin content. For example, these modalities can tell when there is swelling that is affecting the movement of water, which may be indicative of a process that would affect myelin, but they cannot give specific information about the amount of myelin surrounding a nerve. An emerging multicomponent relaxometry technique, termed multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), provides a voxel-wise estimation ranging from 0 to 1 for myelin content, with higher values providing an indirect marker of greater myelin integrity. Two studies have shown increased myelin after injury in football and ice hockey players.8 DTI, which primarily gives information about the myelin-axon bundle interactions, has shown decreased fractional anisotropy after mTBI,myelin-axon bundle interactions, has shown decreased fractional anisotropy after mTBI, indicating that the myelin that is present is less organized.8 Combining mcDESPOT and DTI findings, it is possible to see a more nuanced picture of the remyelination process after mTBI. In the present program, the investigators propose adding the mcDESPOT sequence to the MRI scanner in accordance with the MRI manufacturer's technical requirements. Although the sequences obtained for mcDESPOT are nearly identical sequences used in clinical practice, the flip-angles are changed so that they cannot be read like a traditional image.

Rather, the data have to be post-processed by a computer in order to be able to derive myelin information. The mcDESPOT sequences are FDA approved, and present no additional risk over traditional clinical MRI sequences. Apolipoprotein E (ApoE) is a class of proteins involved in the metabolism of fats in the body, and is important in Alzheimer's disease and cardiovascular disease. How the body makes this protein is genetically coded in the APoE gene. One form of this gene, APoE allele 4 (APoE4) is found in about 25% of the population, but in 60% of patients with Alzheimer's dementia. Infants with this allele also show decreased myelination at a young age. It is postulated that this defect affects the brain's ability to myelinate and remyelinate, leading to decreased or disorganized myelination, which then leads to an increased risk for development of dementia. This study aims to build upon preliminary data collected by the principal investigator (PI) showing increased but disorganized myelin in collegiate football players, by confirming and reproducing these results in a larger population. This study will also add the component of genetic testing for the APoE4 allele to see if there is a sub-segment of the study population that may be at increased risk for brain injury after mTBI and subsequent findings in the research scans. The mcDESPOT and genetic testing findings will also be correlated with routine neuropsychology concussion assessment results.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population High school age (9th-12th grade), male, right-handed Diagnosed with concussion or mild traumatic brain injury
Condition Traumatic Brain Injury
Intervention Device: McDESPOT
myelin specific MRI sequence (mcDESPOT) added to standard MRI sequence
Study Groups/Cohorts
  • mTBI Study Group with McDESPOT sequence
    Study group (30 subjects) of football players diagnosed with mTBI (scan at diagnosis, 3-month follow-up scan, genetic screening, concussion assessment at both interaction)
    Intervention: Device: McDESPOT
  • Control Group
    Control group (30 subjects) of age match non-contact sport players (scan, genetic testing, concussion assessment)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Terminated
Actual Enrollment
 (submitted: September 23, 2020)
13
Original Estimated Enrollment
 (submitted: October 4, 2018)
60
Actual Study Completion Date August 12, 2020
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Experimental Group

    • Patient age range: 9th through 12th grade (high school)
    • Male
    • Right-handed
    • Diagnosis of mTBI or concussion during a football game or training
    • No significant co-morbidities
    • Able to get an MRI
    • Potential subject must be capable of giving informed consent or assent when applicable

      • Control Group

    • Patient age range: 9th through 12th grade (high school)
    • Male Right-handed
    • Does not play contact sports (football, soccer, lacrosse)
    • No significant co-morbidities
    • Able to get an MRI
    • Potential subject must be capable of giving informed consent or assent when applicable

Exclusion Criteria:

  • Unable to tolerate MRI scan
Sex/Gender
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Male high school football players
Ages 13 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers Not Provided
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03698747
Other Study ID Numbers MTBI
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Memorial Healthcare System
Study Sponsor Memorial Healthcare System
Collaborators Not Provided
Investigators
Principal Investigator: Heather Spader, MD Memorial Healthcare System
PRS Account Memorial Healthcare System
Verification Date September 2020