Repetitive Head ImpactsNCT07010887
RHI Interval Effects on Brain Health
A study testing Short Interval, Long Interval and BrainScope qEEG in people with Repetitive Head Impacts, run by Indiana University at 1 site in United States.
Trial summary
Military service members frequently experience repetitive insults or impacts to the head (RHIs). The purpose of the proposed randomized controlled trial is to understand how time intervals affect neurological responses to repetitive subconcussive head impacts. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Repetitive Head Impacts
- What is being tested?
- Short Interval, Long Interval and BrainScope qEEG
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2025to Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Current soccer player (intercollegiate, club, intramural, recreational).
- At least 5 years of soccer heading experience (justification below).
- Ability to provide informed consent without a legally authorized representative (LAR).
Who cannot join
- Any head, neck, or face injury within the 6 months prior to enrollment, including concussions, that precludes participation in contact sports.
- Participants with eye conditions or diseases that could impact the blood vessels in the eye -such as but not limited to: glaucoma, macular degeneration, diabetic retinopathy.
- Determination that the participant is unsuitable for study entry or potentially unable to complete all aspects of the study based on the judgement of the Investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Indiana University School of Public Health
Bloomington, Indiana, 47405
Keisuke Kawata, 812-855-5244, kkawata@iu.edu
Keisuke Kawata, PhD
About this study
Official title: Defining the Role of Repetitive Head Impact Time Intervals in Mitigating Subconcussive Neural Injury
Military service members frequently experience repetitive insults or impacts to the head (RHIs). The purpose of the proposed randomized controlled trial is to understand how time intervals affect neurological responses to repetitive subconcussive head impacts.
Read the detailed description
This study will address whether, and to what extent, the interval of time between repetitive head impact (RHI) clusters (short, 24 hours; long, 72 hours) influences neuronal cellular, physiological, and functional integrity. We will leverage a human laboratory model of RHI to standardize and isolate the effects of RHI in the context of direction, magnitude, and frequency of head impact.
There are three aims that navigate this study:
Aim 1: To determine the effect of the interval of time between RHI clusters on neural cellular and molecular integrities through expression profiles of biofluid proteomic and transcriptomic biomarkers.
Hypotheses: Significant elevations in proteomic biomarkers will be observed acutely after experiencing RHI, and there will be cumulative increase in these biomarkers after 4 weeks of consistent exposure to RHI. The shorter interval of RHI clusters will yield greater degrees of biomarker changes as compared to the longer interval.
Aim 2: To examine the effect of the interval of time between RHI clusters on retinal and ocular-motor health, as assessed by retinal changes on optical coherence tomography (OCT), convergence, and pupillometry.
Hypotheses: A shorter interval of RHI clusters will result in altered retinal coherence and declines in convergence and choice reaction time compared to a longer interval. After 4 weeks of recurring exposure to RHI, declines in retinal and ocular-motor health will persist for 2-week post RHI exposure in the shorter-interval group, but the longer-interval group will normalize by the 2-week post-RHI follow-up.
Aim 3: To determine the influence of the interval of time between RHI clusters in neuronal network as assessed by quantitative EEG and choice reaction time.
Hypotheses: A shorter interval of RHI clusters will induce greater changes in EEG output acutely and chronically after RHI exposure, compared to the longer interval. Changes in EEG signals will persist for 2-week post RHI exposure in the shorter interval, but the changes will be normalized in the longer-interval group.
- Conditions
- Repetitive Head Impacts
- Being tested
- Short Interval, Long Interval, BrainScope qEEG
- Keywords
- Subconcussive brain injury, TBI, Soccer Heading, Time Interval
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short IntervalOther
A standardized and reliable soccer heading protocol will be used for the experiment. Participants perform 16 headers or kicking with 1 header per 30 seconds. The sessions (twice per week for 4 weeks) will be separated by 24 hours.
Long IntervalOther
A standardized and reliable soccer heading protocol will be used for the experiment. Participants perform 16 headers or kicking with 1 header per 30 seconds. The sessions (twice per week for 4 weeks) will be separated by 72 hours.
BrainScope qEEGDevice
An Investigational version of the BrainScope FDA-cleared qEEG acquisition device will be used in this study. The investigational nature of the device is simply based on the code which does not produce a diagnostic result for the blinded researcher. Electrodes will be placed around the participant's forehead and scalp to acquire electrical readings of brain activity.
| Study group | Role | What they receive |
|---|---|---|
| Short Interval - heading | Experimental | Participants in the heading group will undergo 16 soccer headings, twice per week, with 24 hours in between each session. Receives: Other: Short Interval; Device: BrainScope qEEG |
| Long Interval - heading | Experimental | Participants in the heading group will undergo 16 soccer headings, twice per week, with 72 hours in between each session. Receives: Other: Long Interval; Device: BrainScope qEEG |
| Short Interval - kicking | Sham comparator | Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 24 hours in between each session. Receives: Other: Short Interval; Device: BrainScope qEEG |
| Long Interval - kicking | Sham comparator | Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 72 hours in between each session. Receives: Other: Long Interval; Device: BrainScope qEEG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Biomarkers - NfL
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically NF-L (neurofilament light).
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Blood Biomarkers - GFAP
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically GFAP (glial fibrillary acidic protein; nanograms per milliliter).
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Blood Biomarkers - pTau
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically phosphorylated tau (picogram per milliliter).
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Optical Coherence Tomography/Angiography (OCT/A) 1
Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be macula CSF thickness (an indicator of the gain or loss of neurons or glia in the inner nuclear, ganglion cell and nerve fiber layer). Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Optical Coherence Tomography/Angiography (OCT/A) 2
Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be cup-to-disc ratio (an indicator of neurodegeneration at the optic disc).
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Optical Coherence Tomography/Angiography (OCT/A) 3
Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus. The primary OCT/A variable examined will be foveal avascular zone (FAZ) area reflecting the size of the central portion of the macula which contains no blood vessels, and which increases in size with loss of capillaries in the surrounding region).
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Quantitative Electroencephalography (qEEG)
An Investigational version of the BrainScope FDA-cleared qEEG acquisition device will be used in this study. The investigational nature of the device is simply based on the code which does not produce a diagnostic result for the blinded researcher. Thus, the manufacturer's full device indications/labeling document will be the same as the FDA-cleared version. An eyes-closed resting EEG will be recorded. An FDA cleared multivariate EEG marker of concussion, the Concussion Index (CI) will be used as input for this study modeling. The CI includes measures of power (absolute and relative), mean frequency, connectivity (asymmetry, coherence, phase lag, phase synchrony), complexity (fractal dimension and scale-free activity), and information theory (entropy), across and within frequency bands. Other features of interest will be included in the EEG data set. We will use all variables in a single model to analyze which variable, to what extent, contributed to group differences.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Secondary outcomes (9)
Near Point of Convergence (NPC)
NPC will also be assessed on the BrainScope qEEG device. The automatic NPC measurement is administered in the same manner as the manual NPC test and takes less than a minute to perform. The participant focuses on the target at arm's length and slowly brings it toward the tip of their nose. The participant is instructed to stop moving the target when they see two distinct images or when the examiner observes an outward deviation of one eye. Blurring of the image is ignored. The distance between the target and the tip of the participant's nose is recorded in centimeters (cm), digitally and accurately computed by the BrainScope automated ocular function measurement (AOFM) feature.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 1
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Initial pupil diameter (maximum) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 2
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Ending diameter (minimum) is another outcome.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 3
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Latency (time of onset of constriction following light stimulus) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 4
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Constriction velocity (average) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 5
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Maximum constriction velocity (average) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 6
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Dilation velocity (average) velocity (average) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity7
Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. T75 (time to reach 75% of original pupil baseline after peak constriction) is one of our outcomes.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Choice Reaction Time (CRT)
CRT will also be assessed on the BrainScope qEEG device. CRT task includes a rule-based response instruction where the participant presses the right key for one set of numbers and the left key for the other set. Participants are instructed to respond quickly and accurately.
Measured: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2025
- Study start5 Aug 2025
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Repetitive Head ImpactsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The short interval group will be assigned to undergo 16 soccer headings twice per week, with 24 hours in between each heading session. The long interval group will be assigned to undergo 16 soccer headings twice per week, with 72 hours in between each heading session. The control group that perform soccer kicking, instead of heading, will also have long and short intervals, identical to the heading group.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, University of Rochester, Boston Children's Hospital, University at Buffalo
- Responsible party
- Principal investigator, Keisuke Kawata, Indiana University
- Investigators
- Keisuke Kawata, PhD, Principal investigator, Indiana University Bloomington Department of Kineseology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07010887
- Sponsor's protocol ID
- 24461
- Status last verified
- Apr 2026
- First submitted
- 30 May 2025
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D. Consequences of repeated blood-brain barrier disruption in football players. PLoS One. 2013;8(3):e56805. doi: 10.1371/journal.pone.0056805. Epub 2013 Mar 6.
PubMed 23483891Kawata K, Rubin LH, Takahagi M, Lee JH, Sim T, Szwanki V, Bellamy A, Tierney R, Langford D. Subconcussive Impact-Dependent Increase in Plasma S100beta Levels in Collegiate Football Players. J Neurotrauma. 2017 Jul 15;34(14):2254-2260. doi: 10.1089/neu.2016.4786. Epub 2017 Apr 27.
PubMed 28181857Puvenna V, Brennan C, Shaw G, Yang C, Marchi N, Bazarian JJ, Merchant-Borna K, Janigro D. Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits. PLoS One. 2014 May 7;9(5):e96296. doi: 10.1371/journal.pone.0096296. eCollection 2014.
PubMed 24806476Oliver JM, Jones MT, Kirk KM, Gable DA, Repshas JT, Johnson TA, Andreasson U, Norgren N, Blennow K, Zetterberg H. Serum Neurofilament Light in American Football Athletes over the Course of a Season. J Neurotrauma. 2016 Oct 1;33(19):1784-1789. doi: 10.1089/neu.2015.4295. Epub 2016 Mar 16.
PubMed 26700106Oliver JM, Anzalone AJ, Stone JD, Turner SM, Blueitt D, Garrison JC, Askow AT, Luedke JA, Jagim AR. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29;130(5):1655-1662. doi: 10.3171/2017.12.JNS172035. Print 2019 May 1.
PubMed 29807487Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017 May 9;88(19):1788-1794. doi: 10.1212/WNL.0000000000003912. Epub 2017 Apr 12.
PubMed 28404801Joseph JR, Swallow JS, Willsey K, Lapointe AP, Khalatbari S, Korley FK, Oppenlander ME, Park P, Szerlip NJ, Broglio SP. Elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high-school football athletes. J Neurosurg. 2018 Jul 3;130(5):1642-1648. doi: 10.3171/2017.12.JNS172386. Print 2019 May 1.
PubMed 29966462Tierney GJ, Higgins B. The incidence and mechanism of heading in European professional football players over three seasons. Scand J Med Sci Sports. 2021 Apr;31(4):875-883. doi: 10.1111/sms.13900. Epub 2021 Jan 18.
PubMed 33280186Peek K, Vella T, Meyer T, Beaudouin F, McKay M. The incidence and characteristics of purposeful heading in male and female youth football (soccer) within Australia. J Sci Med Sport. 2021 Jun;24(6):603-608. doi: 10.1016/j.jsams.2020.12.010. Epub 2020 Dec 26.
PubMed 33414022Russell ER, Mackay DF, Stewart K, MacLean JA, Pell JP, Stewart W. Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players. JAMA Neurol. 2021 Sep 1;78(9):1057-1063. doi: 10.1001/jamaneurol.2021.2403.
PubMed 34338724Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. N Engl J Med. 2019 Nov 7;381(19):1801-1808. doi: 10.1056/NEJMoa1908483. Epub 2019 Oct 21.
PubMed 31633894Kawata K, Tierney R, Phillips J, Jeka JJ. Effect of Repetitive Sub-concussive Head Impacts on Ocular Near Point of Convergence. Int J Sports Med. 2016 May;37(5):405-10. doi: 10.1055/s-0035-1569290. Epub 2016 Feb 9.
PubMed 26859643
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the Role of Repetitive Head Impact Time Intervals in Mitigating Subconcussive Neural Injury
- ClinicalTrials.gov ID
- NCT07010887
- Acronym / sponsor ID
- 24461
- Conditions
- Repetitive Head Impacts
- Keywords
- Subconcussive brain injury, TBI, Soccer Heading, Time Interval
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense, University of Rochester, Boston Children's Hospital, University at Buffalo
- Study start
- 5 Aug 2025 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 8 Jun 2025 (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.
Military service members frequently experience repetitive insults or impacts to the head (RHIs). The purpose of the proposed randomized controlled trial is to understand how time intervals affect neurological responses to repetitive subconcussive head impacts.
Detailed description
This study will address whether, and to what extent, the interval of time between repetitive head impact (RHI) clusters (short, 24 hours; long, 72 hours) influences neuronal cellular, physiological, and functional integrity. We will leverage a human laboratory model of RHI to standardize and isolate the effects of RHI in the context of direction, magnitude, and frequency of head impact.
There are three aims that navigate this study:
Aim 1: To determine the effect of the interval of time between RHI clusters on neural cellular and molecular integrities through expression profiles of biofluid proteomic and transcriptomic biomarkers.
Hypotheses: Significant elevations in proteomic biomarkers will be observed acutely after experiencing RHI, and there will be cumulative increase in these biomarkers after 4 weeks of consistent exposure to RHI. The shorter interval of RHI clusters will yield greater degrees of biomarker changes as compared to the longer interval.
Aim 2: To examine the effect of the interval of time between RHI clusters on retinal and ocular-motor health, as assessed by retinal changes on optical coherence tomography (OCT), convergence, and pupillometry.
Hypotheses: A shorter interval of RHI clusters will result in altered retinal coherence and declines in convergence and choice reaction time compared to a longer interval. After 4 weeks of recurring exposure to RHI, declines in retinal and ocular-motor health will persist for 2-week post RHI exposure in the shorter-interval group, but the longer-interval group will normalize by the 2-week post-RHI follow-up.
Aim 3: To determine the influence of the interval of time between RHI clusters in neuronal network as assessed by quantitative EEG and choice reaction time.
Hypotheses: A shorter interval of RHI clusters will induce greater changes in EEG output acutely and chronically after RHI exposure, compared to the longer interval. Changes in EEG signals will persist for 2-week post RHI exposure in the shorter interval, but the changes will be normalized in the longer-interval group.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- The short interval group will be assigned to undergo 16 soccer headings twice per week, with 24 hours in between each heading session. The long interval group will be assigned to undergo 16 soccer headings twice per week, with 72 hours in between each heading session. The control group that perform soccer kicking, instead of heading, will also have long and short intervals, identical to the heading group.
| Arm | Type | Receives |
|---|---|---|
| Short Interval - heading | Experimental | Other: Short Interval, Device: BrainScope qEEGParticipants in the heading group will undergo 16 soccer headings, twice per week, with 24 hours in between each session. |
| Long Interval - heading | Experimental | Other: Long Interval, Device: BrainScope qEEGParticipants in the heading group will undergo 16 soccer headings, twice per week, with 72 hours in between each session. |
| Short Interval - kicking | Sham comparator | Other: Short Interval, Device: BrainScope qEEGParticipants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 24 hours in between each session. |
| Long Interval - kicking | Sham comparator | Other: Long Interval, Device: BrainScope qEEGParticipants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 72 hours in between each session. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Current soccer player (intercollegiate, club, intramural, recreational).
- At least 5 years of soccer heading experience (justification below).
- Ability to provide informed consent without a legally authorized representative (LAR).
Key exclusion criteria (3 listed)
- Any head, neck, or face injury within the 6 months prior to enrollment, including concussions, that precludes participation in contact sports.
- Participants with eye conditions or diseases that could impact the blood vessels in the eye -such as but not limited to: glaucoma, macular degeneration, diabetic retinopathy.
- Determination that the participant is unsuitable for study entry or potentially unable to complete all aspects of the study based on the judgement of the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Short IntervalA standardized and reliable soccer heading protocol will be used for the experiment. Participants perform 16 headers or kicking with 1 header per 30 seconds. The sessions (twice per week for 4 weeks) will be separated by 24 hours. | Other | Short Interval - heading, Short Interval - kicking |
| Long IntervalA standardized and reliable soccer heading protocol will be used for the experiment. Participants perform 16 headers or kicking with 1 header per 30 seconds. The sessions (twice per week for 4 weeks) will be separated by 72 hours. | Other | Long Interval - heading, Long Interval - kicking |
| BrainScope qEEGAn Investigational version of the BrainScope FDA-cleared qEEG acquisition device will be used in this study. The investigational nature of the device is simply based on the code which does not produce a diagnostic result for the blinded researcher. Electrodes will be placed around the participant's forehead and scalp to acquire electrical readings of brain activity. | Device | Long Interval - heading, Long Interval - kicking, Short Interval - heading, Short Interval - kicking |
Primary outcome
Blood Biomarkers - NfL
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically NF-L (neurofilament light).
Blood Biomarkers - GFAP
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically GFAP (glial fibrillary acidic protein; nanograms per milliliter).
Blood Biomarkers - pTau
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically phosphorylated tau (picogram per milliliter).
Optical Coherence Tomography/Angiography (OCT/A) 1
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be macula CSF thickness (an indicator of the gain or loss of neurons or glia in the inner nuclear, ganglion cell and nerve fiber layer). Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus.
Optical Coherence Tomography/Angiography (OCT/A) 2
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be cup-to-disc ratio (an indicator of neurodegeneration at the optic disc).
Optical Coherence Tomography/Angiography (OCT/A) 3
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus. The primary OCT/A variable examined will be foveal avascular zone (FAZ) area reflecting the size of the central portion of the macula which contains no blood vessels, and which increases in size with loss of capillaries in the surrounding region).
Quantitative Electroencephalography (qEEG)
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
An Investigational version of the BrainScope FDA-cleared qEEG acquisition device will be used in this study. The investigational nature of the device is simply based on the code which does not produce a diagnostic result for the blinded researcher. Thus, the manufacturer's full device indications/labeling document will be the same as the FDA-cleared version. An eyes-closed resting EEG will be recorded. An FDA cleared multivariate EEG marker of concussion, the Concussion Index (CI) will be used as input for this study modeling. The CI includes measures of power (absolute and relative), mean frequency, connectivity (asymmetry, coherence, phase lag, phase synchrony), complexity (fractal dimension and scale-free activity), and information theory (entropy), across and within frequency bands. Other features of interest will be included in the EEG data set. We will use all variables in a single model to analyze which variable, to what extent, contributed to group differences.
9 secondary outcomes
Near Point of Convergence (NPC)
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 1
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 2
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 3
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 4
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 5
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity 6
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Pupillary Size Measurement and Reactivity7
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
Choice Reaction Time (CRT)
Time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session
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 4 May 2026.
- Background: PubMed 23483891Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D. Consequences of repeated blood-brain barrier disruption in football players. PLoS One. 2013;8(3):e56805. doi: 10.1371/journal.pone.0056805. Epub 2013 Mar 6.
- Background: PubMed 28181857Kawata K, Rubin LH, Takahagi M, Lee JH, Sim T, Szwanki V, Bellamy A, Tierney R, Langford D. Subconcussive Impact-Dependent Increase in Plasma S100beta Levels in Collegiate Football Players. J Neurotrauma. 2017 Jul 15;34(14):2254-2260. doi: 10.1089/neu.2016.4786. Epub 2017 Apr 27.
- Background: PubMed 24806476Puvenna V, Brennan C, Shaw G, Yang C, Marchi N, Bazarian JJ, Merchant-Borna K, Janigro D. Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits. PLoS One. 2014 May 7;9(5):e96296. doi: 10.1371/journal.pone.0096296. eCollection 2014.
- Background: PubMed 26700106Oliver JM, Jones MT, Kirk KM, Gable DA, Repshas JT, Johnson TA, Andreasson U, Norgren N, Blennow K, Zetterberg H. Serum Neurofilament Light in American Football Athletes over the Course of a Season. J Neurotrauma. 2016 Oct 1;33(19):1784-1789. doi: 10.1089/neu.2015.4295. Epub 2016 Mar 16.
- Background: PubMed 29807487Oliver JM, Anzalone AJ, Stone JD, Turner SM, Blueitt D, Garrison JC, Askow AT, Luedke JA, Jagim AR. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29;130(5):1655-1662. doi: 10.3171/2017.12.JNS172035. Print 2019 May 1.
- Background: PubMed 28404801Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017 May 9;88(19):1788-1794. doi: 10.1212/WNL.0000000000003912. Epub 2017 Apr 12.
- Background: PubMed 29966462Joseph JR, Swallow JS, Willsey K, Lapointe AP, Khalatbari S, Korley FK, Oppenlander ME, Park P, Szerlip NJ, Broglio SP. Elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high-school football athletes. J Neurosurg. 2018 Jul 3;130(5):1642-1648. doi: 10.3171/2017.12.JNS172386. Print 2019 May 1.
- Background: PubMed 33280186Tierney GJ, Higgins B. The incidence and mechanism of heading in European professional football players over three seasons. Scand J Med Sci Sports. 2021 Apr;31(4):875-883. doi: 10.1111/sms.13900. Epub 2021 Jan 18.
- Background: PubMed 33414022Peek K, Vella T, Meyer T, Beaudouin F, McKay M. The incidence and characteristics of purposeful heading in male and female youth football (soccer) within Australia. J Sci Med Sport. 2021 Jun;24(6):603-608. doi: 10.1016/j.jsams.2020.12.010. Epub 2020 Dec 26.
- Background: PubMed 34338724Russell ER, Mackay DF, Stewart K, MacLean JA, Pell JP, Stewart W. Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players. JAMA Neurol. 2021 Sep 1;78(9):1057-1063. doi: 10.1001/jamaneurol.2021.2403.
- Background: PubMed 31633894Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. N Engl J Med. 2019 Nov 7;381(19):1801-1808. doi: 10.1056/NEJMoa1908483. Epub 2019 Oct 21.
- Background: PubMed 26859643Kawata K, Tierney R, Phillips J, Jeka JJ. Effect of Repetitive Sub-concussive Head Impacts on Ocular Near Point of Convergence. Int J Sports Med. 2016 May;37(5):405-10. doi: 10.1055/s-0035-1569290. Epub 2016 Feb 9.
- Individual participant dataSharing planned: No
Related trials for Repetitive Head Impacts
RecruitingPhase 1
Monitoring Patients With Repetitive Head Impact With Gamma-glutamylcysteine Supplementation
Repetitive Head Impacts
Enrolling by invitationObservational study
The DIAGNOSE CTE Research Project-II
Chronic Traumatic Encephalopathy (CTE), Alzheimer Disease
Enrolling by invitation
Monitoring & Mitigation of Neurologic Injuries to Optimize Resilience After Repetitive Head Impacts
Head Injuries
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.
Keisuke Kawata, PhD principal investigator
Indiana University Bloomington Department of Kineseology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Short Interval, Long Interval and BrainScope qEEG in people with Repetitive Head Impacts, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Keisuke Kawata, PhD (812-855-5244, kkawata@indiana.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Biomarkers - NfL (time frame: Baseline, 24 hours following the final heading session, 14 days following the final heading session). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07010887, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.