Brain Imaging for Concussion in Former NFL Players

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the long-term brain health of former NFL players who have experienced concussions. Researchers use advanced brain imaging techniques, including [11C] PiB, [18F] Flortaucipir, and [18F] PBR111, to understand how these injuries might affect cognitive functioning over time. The trial invites former NFL players who have retired and experienced concussions, as well as healthy males with no history of contact sports, to participate. The study aims to inform future treatments for those at risk of brain health issues due to sports-related concussions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights into brain health.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that [11C] PiB effectively images amyloid deposits in the brain, particularly in patients with traumatic brain injury (TBI). Researchers have used this tracer safely in various settings, with no significant side effects reported.

Research indicates that [18F] Flortaucipir is well-tolerated in older adults, including those with head injuries. This tracer helps detect tau protein build-up, linked to Alzheimer's disease and other conditions, without highlighting any major safety concerns.

For [18F] PBR111, specific data is limited. However, PET tracers like [18F] PBR111 are generally considered safe in medical imaging. As this trial is in its early phase, the primary goal is to assess the safety and tolerability of these tracers.

Overall, studies suggest that these imaging tracers are well-tolerated in humans, but the trial will further investigate their safety in former NFL players. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses advanced brain imaging techniques with [11C] PiB, [18F] Flortaucipir, and [18F] PBR111 to study concussions in former NFL players. Unlike traditional methods that rely heavily on cognitive testing and subjective assessments, these imaging agents can potentially provide a clearer picture of brain changes by highlighting abnormal protein deposits associated with concussion-related brain damage. This approach could lead to more precise diagnosis and better understanding of how repeated head injuries affect brain health over time, paving the way for targeted treatments in the future.

What evidence suggests that this trial's treatments could be effective for concussions in former NFL players?

In this trial, [11C] PiB, [18F] Flortaucipir, and [18F] PBR111 study brain changes in former NFL players with different cognitive functions and concussion histories. Research has shown that [11C] PiB effectively identifies amyloid deposits in the brain, linked to traumatic brain injuries (TBI). This compound adheres more to areas with amyloid build-up, aiding in detecting brain changes after concussions. Studies have found that [18F] Flortaucipir detects tau protein build-up in the brain, another marker often seen in brain injuries and conditions like chronic traumatic encephalopathy (CTE). Meanwhile, researchers have studied [18F] PBR111 as a method to track brain swelling after repeated head injuries. Together, these imaging agents provide important insights into brain changes related to concussions, helping researchers understand their long-term effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Michael McCrea, PhD

Principal Investigator

Medical College of Wisconsin

Jason Mihalik, PhD

Principal Investigator

University of North Carolina, Chapel Hill

William Meehan, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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

I am between 50 and 70 years old.

Retired from professional football

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/24217171/

Amyloid Imaging With Carbon 11-labeled Pittsburgh ... - PubMed

[11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4084932/

Amyloid Imaging With Carbon 11–Labeled Pittsburgh ...

Carbon 11–Labeled Pittsburgh Compound B ([11C]PiB) Distribution Volume Ratio (DVR) Maps From a Control and 3 Patients With Traumatic Brain Injury (TBI). Figure ...

3.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00831/full

[ 18 F]FDG, [ 11 C]PiB, and [ 18 F]AV-1451 PET Imaging of ...

We have initiated a protocol for in vivo imaging of patients with suspected TBI-related neurodegeneration utilizing volumetric MRI and PET studies.

4.

researchgate.net

researchgate.net/publication/258444836_Amyloid_Imaging_With_Carbon_11-Labeled_Pittsburgh_Compound_B_for_Traumatic_Brain_Injury

(PDF) Amyloid Imaging With Carbon 11-Labeled Pittsburgh ...

[11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) ...

5.

jnm.snmjournals.org

jnm.snmjournals.org/content/48/4/547

Visual Assessment Versus Quantitative ...

11 C-PIB PET images appear easier to read and more accurate than 18 F-FDG PET images in AD diagnosis, particularly in older subjects.

6.

medrxiv.org

medrxiv.org/content/10.1101/2023.11.30.23298528v1.full

Traumatic brain injury and Alzheimer's Disease biomarkers

The Aβ tracers include Pittsburgh Compound B ([C]-PiB ... 11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder.

7.

repository.cam.ac.uk

repository.cam.ac.uk/bitstreams/dc822aa5-f988-45e9-addc-1a6dcb9874df/download

Imaging amyloid beta deposition following traumatic brain ...

Methods: We undertook [11C]PIB PET to image amyloid deposition in 11 controls (median [range] age. 35 [24-60] y), and in 15 patients (33 [21-50] y), ...

8.

empr.com

empr.com/home/news/drug-news/11cpib-pet-can-image-amyloid-deposits-after-tbi/

[ 11 C]PiB PET Can Image Amyloid Deposits After TBI

The researchers found that patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the ...