Brain Imaging for Concussion in Former NFL Players

Recruiting at 2 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Moderate TBI, Psychotic Disorder, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this 5-year prospective research study is to characterize the association between concussions, sub-concussive exposure, and long-term neurologic health outcomes in former NFL players. To achieve the study aims, the investigators will conduct detailed research visits that include clinical outcome assessments, blood-based biomarkers, advanced magnetic resonance imaging (MRI), positron emission tomography (PET) using investigational tracers and genetic testing. Ultimately, the goal of this study is to translate the findings from this study into clinical, interventional studies for at risk former NFL players.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

What data supports the effectiveness of the drug [11C] PiB, [18F] Flortaucipir, [18F] PBR111 for brain imaging in former NFL players with concussions?

Some studies suggest that the drug [18F]-Flortaucipir (FTP) may help detect certain brain changes related to chronic traumatic encephalopathy (CTE) in living former football players, although its effectiveness for clinical evaluation in this population is still uncertain. ^{1 2 3 4 5}

Is the brain imaging treatment safe for humans?

The brain imaging treatment using [18F] Flortaucipir has been used in studies with former football players and adults at risk for Alzheimer's, and no significant safety concerns have been reported in these studies. ^{1 4 5 6 7}

How does the treatment in the Brain Imaging for Concussion in Former NFL Players trial differ from other treatments for concussions?

The treatment in this trial is unique because it focuses on using advanced brain imaging techniques, like PET scans with specific tracers, to detect changes in the brain associated with concussions, rather than relying on traditional symptom-based assessments. This approach aims to provide a more precise understanding of brain changes in former NFL players, which is not typically addressed by standard concussion treatments. ^{2 4 5 8 9}

Research Team

William Meehan, MD

Principal Investigator

Boston Children's Hospital

Michael McCrea, PhD

Principal Investigator

Medical College of Wisconsin

Jason Mihalik, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This study is for former NFL players aged between 50-70 who have retired from professional football and have at least one year of NFL experience. It's also for individuals without prior exposure to football or other collision sports and concussions, matched by age and intellectual functioning to the player group.

Inclusion Criteria

I am between 50 and 70 years old.

I have never played football, collision sports, or had a concussion.

Retired from professional football

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phone screening with Brief Test of Adult Cognition by Telephone (BTACT)

In-Person Neurobiopsychosocial Research Evaluation 1

Participants undergo a detailed neuropsychological assessment, patient-reported outcomes, and symptom validity measures, including proteomic and genomic studies, MRI, and PET imaging

1-2 weeks

1 visit (in-person)

Annual Follow-Up

Annual follow-up surveys of health status and life function are administered for 5 years

5 years

Annual surveys (remote)

In-Person Neurobiopsychosocial Research Evaluation 2

A subset of participants return for a second research assessment of neurobiopsychosocial function

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• [11C] PiB
• [18F] Flortaucipir
• [18F] PBR111

Trial Overview The trial is examining how concussions affect long-term brain health in ex-NFL players using advanced MRI, PET scans with new tracers ([18F] PBR111, [18F] Flortaucipir, [11C] PiB), blood tests for biomarkers, and genetic testing over a five-year period.

Participant Groups

Group I: Medium Cognitive Functioning/Medium Concussion History Experimental Treatment 3 Interventions

Former NFL Players with medium cognitive functioning and medium concussion history with be included in this group.

Group II: Medium Cognitive Functioning/Low Concussion History Experimental Treatment 3 Interventions

Former NFL Players with medium cognitive functioning and low concussion history with be included in this group.

Group III: Medium Cognitive Functioning/High Concussion History Experimental Treatment 3 Interventions

Former NFL Players with medium cognitive functioning and high concussion history with be included in this group.

Group IV: Low Cognitive Functioning/Medium Concussion History Experimental Treatment 3 Interventions

Former NFL players with low cognitive function and medium concussion history will be included in this group.

Group V: Low Cognitive Functioning/Low Concussion History Experimental Treatment 3 Interventions

Former NFL players with low cognitive function and low concussion history will be included in this group.

Group VI: Low Cognitive Functioning/High Concussion History Experimental Treatment 3 Interventions

Former NFL players with low cognitive function and high concussion history will be included in this group.

Group VII: High Cognitive Functioning/Medium Concussion History Experimental Treatment 3 Interventions

Former NFL Players with high cognitive functioning and high concussion history with be included in this group.

Group VIII: High Cognitive Functioning/Low Concussion History Experimental Treatment 3 Interventions

Former NFL players with high cognitive function and low concussion history will be included in this group.

Group IX: High Cognitive Functioning/ High Concussion History Experimental Treatment 3 Interventions

Former NFL players with high cognitive function and high concussion history will be included in this group.

Group X: Healthy Male Controls Experimental Treatment 3 Interventions

Healthy male demographically matched controls will be included in this group.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

National Football League

Collaborator

Trials

8

Recruited

2,000+

Findings from Research

Flortaucipir PET scans can effectively predict near-term clinical progression in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), with 70% of those showing an advanced AD pattern experiencing significant clinical deterioration over 18 months.

The study involved 364 participants, and those with an advanced AD pattern had a higher risk of clinical decline compared to those with a nonadvanced pattern, indicating that these scans can provide valuable prognostic information for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. Lu, M., Pontecorvo, MJ., Devous, MD., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of Shortening the Scan Duration on Quantitative Accuracy of [18F]Flortaucipir Studies. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Dysfunction and Exposure to Head Impacts in University Football Players. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes. [2022]

4. Denmark pubmed.ncbi.nlm.nih.gov

Animal model for sport-related concussion; ICP and cognitive function. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Multiparametric MRI changes persist beyond recovery in concussed adolescent hockey players. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Quantitative dynamic contrast-enhanced MR imaging shows widespread blood-brain barrier disruption in mild traumatic brain injury patients with post-concussion syndrome. [2020]