RHI Interval Effects on Brain Health

NCT ID: NCT07010887

Last Updated: 2025-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-04

Study Completion Date

2028-09-30

Brief Summary

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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

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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

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Repetitive Head Impacts

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
The blood biomarker experimentalist and lead statistician will be masked throughout the trial.

Study Groups

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Short Interval - heading

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

Group Type EXPERIMENTAL

Short Interval

Intervention Type 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.

Long Interval - heading

Participants in the heading group will undergo 16 soccer headings, twice per week, with 72 hours in between each session.

Group Type EXPERIMENTAL

Long Interval

Intervention Type 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.

Short Interval - kicking

Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 24 hours in between each session.

Group Type SHAM_COMPARATOR

Short Interval

Intervention Type 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.

Long Interval - kicking

Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 72 hours in between each session.

Group Type SHAM_COMPARATOR

Long Interval

Intervention Type 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.

Interventions

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Short Interval

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.

Intervention Type OTHER

Long Interval

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role collaborator

University at Buffalo

OTHER

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role lead

Responsible Party

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Keisuke Kawata

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Keisuke Kawata, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University Bloomington Department of Kineseology

Locations

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Indiana University School of Public Health

Bloomington, Indiana, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Keisuke Kawata, PhD

Role: CONTACT

812-855-5244

Blair Johnson, PhD

Role: CONTACT

812-855-8699

Facility Contacts

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Keisuke Kawata

Role: primary

8128555244

References

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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.

Reference Type BACKGROUND
PMID: 23483891 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28181857 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24806476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26700106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29807487 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28404801 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29966462 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33280186 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33414022 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34338724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31633894 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26859643 (View on PubMed)

Other Identifiers

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24461

Identifier Type: -

Identifier Source: org_study_id

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