RHI Interval Effects on Brain Health

NCT07010887 | Recruiting FDA Device

• 1 other identifier: 24461
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Repetitive Head Impacts

Keywords

Subconcussive brain injury; TBI; Soccer Heading; Time Interval

Outcome Measures

Primary Outcomes (7)

• Blood Biomarkers - NfL

  The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically NF-L (neurofilament light).

  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).

  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).

  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.

  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).

  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).

  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.

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

Secondary Outcomes (9)

• Near Point of Convergence (NPC)

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

• Pupillary Size Measurement and Reactivity 1

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

• Pupillary Size Measurement and Reactivity 2

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

• Pupillary Size Measurement and Reactivity 3

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

• Pupillary Size Measurement and Reactivity 4

  Baseline, 24 hours following the final heading session, 14 days following the final heading session

Study Arms (4)

Short Interval - heading

EXPERIMENTAL

Participants in the heading group will undergo 16 soccer headings, twice per week, with 24 hours in between each session.

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.

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.

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.

Other: Long Interval; Device: BrainScope qEEG

Interventions

Short Interval OTHER

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.

Short Interval - heading; Short Interval - kicking

Long Interval OTHER

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.

Long Interval - heading; Long Interval - kicking

BrainScope qEEG DEVICE

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.

Long Interval - heading; Long Interval - kicking; Short Interval - heading; Short Interval - kicking

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University: lead
• United States Department of Defense: collaborator
• University of Rochester: collaborator
• Boston Children's Hospital: collaborator
• University at Buffalo: collaborator

Study Sites (1)

Indiana University School of Public Health

Bloomington, Indiana, 47405, United States

RECRUITING

Related Publications (12)

• 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.

  PMID: 23483891 BACKGROUND

• Kawata 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.

  PMID: 28181857 BACKGROUND

• Puvenna 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.

  PMID: 24806476 BACKGROUND

• Oliver 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.

  PMID: 26700106 BACKGROUND

• Oliver 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.

  PMID: 29807487 BACKGROUND

• Shahim 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.

  PMID: 28404801 BACKGROUND

• Joseph 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.

  PMID: 29966462 BACKGROUND

• Tierney 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.

  PMID: 33280186 BACKGROUND

• Peek 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.

  PMID: 33414022 BACKGROUND

• Russell 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.

  PMID: 34338724 BACKGROUND

• Mackay 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.

  PMID: 31633894 BACKGROUND

• Kawata 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.

  PMID: 26859643 BACKGROUND

Study Officials

• Keisuke Kawata, PhD

  Indiana University Bloomington Department of Kineseology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keisuke Kawata, PhD

CONTACT

812-855-5244; kkawata@indiana.edu

Blair Johnson, PhD

CONTACT

812-855-8699; bj33@iu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The blood biomarker experimentalist and lead statistician will be masked throughout the trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: May 30, 2025
• First Posted: June 8, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)