NFL LONG Prospective Study

Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Neurologic Function Across the Lifespan: A Prospective, LONGitudinal, and Translational Study for Former National Football League Players

ClinicalTrials.gov ID

NCT04263337

Acronym / sponsor ID

19-1065

Conditions

Concussion, Brain

Keywords

Concussion, Former NFL Players, Football, Neurologic, Sub-concussive Exposure

Phase

Phase 1

Study type

Interventional

Recruitment status

Active, not recruiting

Enrolment

250 participants (estimated)

Lead sponsor

University of North Carolina, Chapel HillUniversity, hospital or other

Collaborators

Boston Children's Hospital, Medical College of Wisconsin, National Football League

Study start

12 Mar 2020 (actual)

Primary completion

Aug 2028 (estimated)

Study completion

Aug 2028 (estimated)

First posted

10 Feb 2020 (actual)

Results

Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Basic science

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

10

Who may qualify

Ages

50 to 70 years

Sex

Male only

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. PET Neuroimaging SUVR Over Time

   Time frame: Baseline, up to 3 Year Follow-up

   Positron Emission Tomography (PET) Scan- Standard uptake value ratio (SUVR) of the following tracers: Tau tracer, [18 F]Flortaucipir; AV1415 Amyloid tracer, Pittsburgh compound-B (11C-PiB); Neuroinflammation tracer, [18 F] peripheral benzodiazepine receptor (PBR111)

2. MRI Neuroimaging Over Time

   Time frame: Baseline, up to 3 Year Follow-up

   Advanced MRI Sequence Structural imaging (T1, T2, T2-FLAIR) Tissue/microstructural organization-Diffusion MRI Cerebral blood flow-Arterial Spin Labeling Susceptibility weighted imaging/quantitative susceptibility mapping Functional MRI- resting state functional MRI

3. Serum Biomarkers Over Time

   Time frame: Baseline, up to 3 Year Follow-up

   Blood collection for analysis of serum markers of neurodegenerative disease and neurodegeneration

4. Mean Change in Headache Impact Test (HIT-6)

   Time frame: Baseline, up to 3 Year Follow-up

   The HIT-6 is a screening measure that assesses the degree to which individual's experiences of headaches impacts their ability to perform daily functional roles. The six-items can be responded to in five ways, which include, never (6-points), rarely (8-points), sometimes (10-points), very often (11-points), and always (13-points).

5. Mean Change in MDS-UPDRS Score

   Time frame: Baseline, up to 3 Year Follow-up

   The MDS-UPDRS evaluates motor and non-motor symptoms in persons with Parkinson's and consists of 4 parts with various questions and evaluations. Parts I and II (non-motor) each contain 13 questions/evaluations, Part III (motor) contains 33 and Part IV (motor) contains 6. Each question/evaluation score ranges from 0 (normal) to 4 (severe). Higher scores indicate a greater impact of Parkinson's disease symptoms (i.e., worse symptoms).

6. Mean Change in Postural Stability-Sensory Organization Test

   Time frame: Baseline, up to 3 Year Follow-up

   The stability-sensory organization test is an index obtained by the NeuroCom Balance System. The minimum score is 0 and there is no specified maximum value. A lower score indicates better postural stability. Postural stability is measured utilizing a dynamic force plate to quantify the vertical forces exerted through the patient's feet to measure center of gravity position and postural control.

7. Mean Change in Structured Inventory of Malingered Symptomatology (SIMS)

   Time frame: Baseline, up to 3 Year Follow-up

   A 75 true-or-false item measures that assesses malingering psychopathology and neuropsychological symptoms. The measure provides an overall score for probably malingering, as well as five subscales; including Psychosis, Low Intelligence, Neurologic Impairment, Affective Disorders, and Amnestic Disorders Endorsement of highly atypical symptoms and endorsement pattern profiles, this measure has demonstrated efficacy in differentiating malingerers from true clinical populations.

8. Mean Change in Medical Symptom Validity Test (MSVT)

   Time frame: Baseline, up to 3 Year Follow-up

   The MSVT is measure typically used in the detection of suboptimal effort. The test consists of a process in which participants are asked to learn 10 word pairs and later recall the word pairs. The minimum score is 0% and the maximum value is 100%.

9. Mean Change in National Institute of Health (NIH) Toolbox

   Time frame: Baseline, up to 3 Year Follow-up

   A computerized measure of cognitive functioning across several domains of cognition developed by the NIH. The Toolbox Cognition measure is comprised of several subtests assessing various domains of cognitive functioning. The minimum score is 0 and there is no maximum score.

10. Mean Change in Rey Auditory Verbal Learning Test (RAVLT)

    Time frame: Baseline, up to 3 Year Follow-up

    The RAVLT is a measure of auditory verbal learning, which is commonly affected among individuals with memory and other related cognitive disorders. Subjects are asked the learn and immediately recall a 15-word list across 5 different trials. They are asked to do the same for second, intrusion list, and then they are asked to recall the first list immediately after. Following a 30 minute delay, participants are asked to spontaneously recall the word list. Immediately following the delay recall trial, recognition memory is tested in a yes/no format where subjects are asked to discriminate words from the original list from novel distractors. The minimum score is 0 and the maximum score is 15.

11. Mean Change in Dot Counting Test

    Time frame: Baseline, up to 3 Year Follow-up

    The Dot Counting Test is a measure effort and validity of session results. Within the measure, subjects are essentially asked to count the number of dots on various stimuli pages. Each specific page has a maximum ranging from 7-28 and the minimum score is 0.

12. Mean Change in Delis Kaplan Executive Function System (DKEFS) Verbal Fluency, Trailmaking Test (TMT), and Color-Word Interference

    Time frame: Baseline, up to 3 Year Follow-up

    The DKEFS is a measure that is associated with integrity and functioning of the frontal system of the brain, or executive functioning. Verbal fluency involves administration of 3 trials in which participants generate words based on letter prompts. The minimum score is 0 and there is no maximum. Two additional trials involving generation of word lists based on categories is also included. The DKEFS TMT is a test of speeded sequencing and set-shifting with sensitivity to sport-related concussion. There are 4 trials consisting of psychomotor speed, number sequencing, letter sequencing, and letter-number sequencing/shifting. The minimum is 0 and there is no maximum. DKEFS Color-Word consists of 4 trials in which participants are timed on (1) colors on the page, (2) read words on the page, (3) inhibit responses of words and state colors that items are printed in, and (4) set-shift in their ability to perform number 3 based on different principles. The minimum is 0 and there is no maximum.

13. Mean Change in Satisfaction with Life Scale (SWLS) Score

    Time frame: Baseline, up to 3 Year Follow-up

    Satisfaction with Life Scale is a short 5-item instrument designed to measure global cognitive judgments of satisfaction with one's life. Questions are responded to on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Total scores can be classified at extremely satisfied (31-35), satisfied (26-30), slightly satisfied (21-25), neutral (20), slightly dissatisfied (15-19), dissatisfied (10-14), and extremely dissatisfied (5-9).

14. Mean Change in Alcohol Use Disorders Identification Test (AUDIT) score

    Time frame: Baseline, up to 3 Year Follow-up

    Alcohol Use Disorders Identification Test consists of three domains: Hazardous alcohol use (items 1-3), dependence symptoms (items 4-6), and harmful alcohol use (items 7-10). Participants respond to items on a scale between 0 to 4, and a total score can be calculated based on individual items.

15. Mean Change in PROMIS Cognitive Functioning Score

    Time frame: Baseline, up to 3 Year Follow-up

    The PROMIS Cognitive Function is a self-reported measure that assesses patient-perceived cognitive deficits and the extent to which cognitive impairments interfere with daily functioning. The short-form consists of 4-itens that are scored on a 5-point Likert scale (5-never) to 1 (very often). Raw scores are converted into T-score for each participant. A T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10.

16. Mean Change in WAIS-IV Coding and Symbol Search

    Time frame: Baseline, up to 3 Year Follow-up

    The Coding and Symbol Search subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) are two subtests that make up the Processing Speed Index of the WAIS-IV. Each subtest requires two minutes to complete and ultimately, reflect the participants ability to complete as many items correctly as possible within the time limit. The minimum score is 0 and the maximum is 60 for Symbol Search and 135 for Coding.

17. Mean Change in Neuro-Quality Of Life (QOL): Emotional and Behavioral Dyscontrol

    Time frame: Baseline, up to 3 Year Follow-up

    This is an eight-item measure from the Neuro-QOL set of tools, which assesses various symptoms and behaviors associated with frontal lobe dysfunction, particularly as it relates to disinhibited actions or behaviors. Items are scored on a five-point Likert scale, ranging from 1 (never) to 5 (always). A T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10.

18. Mean Change in Frontal systems behavior scale (FrsBe)

    Time frame: Baseline, up to 3 Year Follow-up

    The FrSBe is a 46-item self-report measure of various symptoms and behaviors commonly associated with executive dysfunction. On a 5-point Likert scale ranging from 1 to 5, participants endorse the degree to which they experience the symptom/behavior before and after the present illness/injury. A total frontal systems score can be calculated for before and after the injury/illness, as well as three subscales of frontal lobe symptoms or behaviors, including apathy, disinhibition, and executive dysfunction. Raw scores are converted into T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10.

19. Mean Change in Everyday Cognition assessment (ECog)

    Time frame: Baseline, up to 3 Year Follow-up

    This measure is intended to be used as a measure of behaviors typically associated with forgetfulness and other cognitive difficulties. This will aid in identifying neurological health difficulties (i.e., cognitive decline) among those individuals who have limited insight on self-report cognitive functioning measures. The ECog Assessment is comprised of 12-items that are rated on a 4-point Likert scale ranging from 1 (better or no change compared to 10 years earlier) to 4 (consistently much worse). Total scores from the measure are calculated by summing responses on all items and dividing by the number of questions answered.

20. Mean Change in Minnesota Multiphasic Personality Inventory (MMPI)-2-RF Cognitive Complaints Scale

    Time frame: Baseline, up to 3 Year Follow-up

    The cognitive complaints scale is a subscale of the derived from the full MMPI-2-RF. As part of the full instrument, the Cognitive Complaints Scale has been used as an embedded measure of symptom validity. In order to avoid administering the full over 500 item instrument, only the 13-itmes from the Cognitive Complaints Scale are administered in isolation for the current study. Items are presented in a true-false format. This method of administration has been performed in a number of studies in the published literature. A T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10.

21. Mean Change in PROMIS_29 Score

    Time frame: Baseline, up to 3 Year Follow-up

    A self-report 29-itme measure of overall functioning. Participants respond on a Likert scale ranging from 5 (without any difficulty) to 1 (unable to do). The measure generates an overall score of functioning, as well as subscales of physical function, anxiety, depression, fatigue, sleep disturbance, able to participate in social roles/activities, pain interference, and pain intensity. Raw scores are converted into T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10.

22. Mean Change in Beck Depression Inventory (BDI-II) Score

    Time frame: Baseline, up to 3 Year Follow-up

    A 21-item measure inquiring about common symptoms of depression. Each item is measured on a scale from 0-3, with higher numbers reflecting a higher-degree of symptomology over the last 2 weeks for that item. Raw scores can be classified into severity categories, including normal (0-13), mild (14-19), moderate (20-28), and severe (29-63).

23. Mean Change in Beck Anxiety Inventory (BAI-II)-Score

    Time frame: Baseline, up to 3 Year Follow-up

    A 21-item measure of common physiological and worry-related symptoms associated with anxiety. Responses are recorded on a 4-point Likert scale ranging from 0 (not at all) to 3 (severely). Raw scores can be classified into severity categories, including minimal anxiety (0-7), mild anxiety (8-15), moderate (16-25), and severe (26-63).

24. Mean Change in Neuropsychiatric Inventory Questionnaire NPI-Q2 Score

    Time frame: Baseline, up to 3 Year Follow-up

    A measure of common dementia-related behavioral symptoms among older adults. Within the measure 12 domains of these symptoms are recorded, including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor activity night-time behavioral disturbances and appetite, and eating abnormalities. A screening question is asked about each sub-domain. If the responses to these questions indicate that the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale.

25. Mean Change in Social Readjustment Rating Scale (SRRS) Score

    Time frame: Baseline, up to 3 Year Follow-up

    This 43-item measure quantifies stress associated with common life events (life changing unit), with a unique value associated with each event over a 12-month period. For example, death of a spouse garners a score of 100 and major holidays equals 11 points. The total number of points is summed and a higher score is representative of a greater degree of life-event related distress. A score of 150 life units or less suggests a 30% change of suffering from stress, 150-299 is associated with a 50% chance of suffering from stress, and over 300 life units suggests that the person has an 8% chance of developing a stress related illness.

26. Mean Change in Ego Resilience Scale (ER89) Score

    Time frame: Baseline, up to 3 Year Follow-up

    This is a 14-item measure used to assess resilience in individuals following stressful events. Items are scored on a 4 point Likert Scale ranging from 1-Does not Apply at All, 2-Applies Slightly, 3-Applies Somewhat, and 4- Applies Very Strongly; and scores for each item are summed to obtain a total score. Higher scores indicate a more favorable outcome

27. Mean Change in Athlete Identity Questionnaire Score

    Time frame: Baseline, up to 3 Year Follow-up

    This questionnaire has been adapted from the previously established "Athletic Identity Measurement Scale" for currently active athletes (not retired). Items are scored on a 7 point Likert Scale ranging from 1-Strongly Disagree to 7-Strongly Agree.

28. Mean Change in Childhood Development and Adversity Questions Score

    Time frame: Baseline, up to 3 Year Follow-up

    This is a 33-item questionnaire that was developed from previous work to give insight into childhood experiences, socioeconomic stability, and other important environmental factors that may influence later-life socioeconomic factors, health, and well-being. The questionnaire contains items pertaining to Social and Community Context (1 item), Economic Stability (4 items), Education Access and Quality (1 item), Health Care Access and Quality (2 items), Neighborhood and Built Environment (3 items), and Adverse Childhood Experiences (Emotional Neglect [6 items], Financial Need [2 items], Parental Intimidation [4 items], Parental Violence [2 items], and Family Problems and Separation [4 items]).

29. Mean Change in International Physical Activity Questionnaire (IPAQ) Score

    Time frame: Baseline, up to 3 Year Follow-up

    This is a 4-item questionnaire intended to obtain data on health-related physical activity. It was developed for both research studies and patient monitoring. Each of the 4 items asks about the number of days per week, and the duration of time in each day participating in different physical activities: vigorous; moderate; walking; and sitting. Answers to these questions will be used to compare to activity recommendations put forth by organizations such as the American College of Sports Medicine.

30. Mean Change in Rapid Eating Assessment for Participants (REAPS) Score

    Time frame: Baseline, up to 3 Year Follow-up

    This is a 16-item questionnaire about the individuals' behaviors regarding food consumption. Participants respond to the first 13 items by selecting from the following options: "Usually/often"; "Sometimes"; "Rarely/Never"; or, when appropriate, a selection that the item does not apply to them. Responses from these first 13 items are then scored and summed into a diet quality score, where the total range of values falls between "13" (lowest quality diet) and "39" (highest quality diet). Items 14 and 15 request "Yes" or "No" responses: 14. "You or a member of your family usually shops and cooks rather than eating sit-down or take-out restaurant food?"; and 15. "Usually feel well enough to shop or cook." The 16th item is answered on a 5-point Likert scale from "1" (Very willing) to "5" (Not at all willing).

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
• Background: PubMed 23902607Randolph C, Karantzoulis S, Guskiewicz K. Prevalence and characterization of mild cognitive impairment in retired national football league players. J Int Neuropsychol Soc. 2013 Sep;19(8):873-80. doi: 10.1017/S1355617713000805. Epub 2013 Aug 1.
• Background: PubMed 16239884Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, Jordan BD. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 Oct;57(4):719-26; discussion 719-26. doi: 10.1093/neurosurgery/57.4.719.
• Background: PubMed 22922518Kerr ZY, Marshall SW, Harding HP Jr, Guskiewicz KM. Nine-year risk of depression diagnosis increases with increasing self-reported concussions in retired professional football players. Am J Sports Med. 2012 Oct;40(10):2206-12. doi: 10.1177/0363546512456193. Epub 2012 Aug 24.
• Background: PubMed 29087238Clark MD, Varangis EML, Champagne AA, Giovanello KS, Shi F, Kerr ZY, Smith JK, Guskiewicz KM. Effects of Career Duration, Concussion History, and Playing Position on White Matter Microstructure and Functional Neural Recruitment in Former College and Professional Football Athletes. Radiology. 2018 Mar;286(3):967-977. doi: 10.1148/radiol.2017170539. Epub 2017 Oct 31.
• Background: PubMed 26193380Meehan WP 3rd, Taylor AM, Berkner P, Sandstrom NJ, Peluso MW, Kurtz MM, Pascual-Leone A, Mannix R. Division III Collision Sports Are Not Associated with Neurobehavioral Quality of Life. J Neurotrauma. 2016 Jan 15;33(2):254-9. doi: 10.1089/neu.2015.3930. Epub 2015 Jul 20.
• Background: PubMed 27364748Mannix R, Meehan WP 3rd, Pascual-Leone A. Sports-related concussions - media, science and policy. Nat Rev Neurol. 2016 Aug;12(8):486-90. doi: 10.1038/nrneurol.2016.99. Epub 2016 Jul 1.
• Background: PubMed 28396360Carson A. Concussion, dementia and CTE: are we getting it very wrong? J Neurol Neurosurg Psychiatry. 2017 Jun;88(6):462-464. doi: 10.1136/jnnp-2016-315510. Epub 2017 Apr 10. No abstract available.
• Background: PubMed 26253448Meehan W 3rd, Mannix R, Zafonte R, Pascual-Leone A. Chronic traumatic encephalopathy and athletes. Neurology. 2015 Oct 27;85(17):1504-11. doi: 10.1212/WNL.0000000000001893. Epub 2015 Aug 7.
• Background: PubMed 28672325Deshpande SK, Hasegawa RB, Rabinowitz AR, Whyte J, Roan CL, Tabatabaei A, Baiocchi M, Karlawish JH, Master CL, Small DS. Association of Playing High School Football With Cognition and Mental Health Later in Life. JAMA Neurol. 2017 Aug 1;74(8):909-918. doi: 10.1001/jamaneurol.2017.1317.
• Background: PubMed 27526721Baugh CM, Kroshus E, Kiernan PT, Mendel D, Meehan WP 3rd. Football Players' Perceptions of Future Risk of Concussion and Concussion-Related Health Outcomes. J Neurotrauma. 2017 Feb 15;34(4):790-797. doi: 10.1089/neu.2016.4585. Epub 2016 Sep 16.
• Background: PubMed 12144861Zemlan FP, Jauch EC, Mulchahey JJ, Gabbita SP, Rosenberg WS, Speciale SG, Zuccarello M. C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res. 2002 Aug 23;947(1):131-9. doi: 10.1016/s0006-8993(02)02920-7.
• Background: PubMed 23684880Van Essen DC, Smith SM, Barch DM, Behrens TE, Yacoub E, Ugurbil K; WU-Minn HCP Consortium. The WU-Minn Human Connectome Project: an overview. Neuroimage. 2013 Oct 15;80:62-79. doi: 10.1016/j.neuroimage.2013.05.041. Epub 2013 May 16.
• Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

3 sites in 1 country: see every site and its status.