RHI Interval Effects on Brain Health

Not Applicable

Not yet recruiting

• Conditions: Repetitive Head Impacts

• Registration Number: NCT07010887
• Lead Sponsor: Indiana University

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.

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 Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-30
• Study First Submitted QC: 2025-05-30
• Last Update Submitted: 2025-05-30
• Study First Posted: 2025-06-08
• Last Update Posted: 2025-06-08
• Study Start: 2025-07-01
• Primary Completion: 2028-05
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 102

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Blood Biomarkers	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), phosphorylated tau (picogram per milliliter), and GFAP (glial fibrillary acidic protein; nanograms per milliliter). The aggregation of all blood biomarkers will provide a comprehensive overview of the biofluid profile of the participant following repetitive head injury.
Optical Coherence Tomography/Angiography (OCT/A)	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), and cup-to-disc ratio (an indicator of neurodegeneration at the optic disc). 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)	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.

Secondary Outcome Measures

Name	Time	Method
Near Point of Convergence (NPC)	Baseline, 24 hours following the final heading session, 14 days following the final heading session	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.
Pupillary Size Measurement and Reactivity	Baseline, 24 hours following the final heading session, 14 days following the final heading session	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. The following pupillometry metrics will be collected: initial pupil diameter (maximum), ending diameter (minimum), latency (time of onset of constriction following light stimulus), constriction velocity (average), maximum constriction velocity, dilation velocity (average) and T75 (time to reach 75% of original pupil baseline after peak constriction).
Choice Reaction Time (CRT)	Baseline, 24 hours following the final heading session, 14 days following the final heading session	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.

Trial Locations

Locations (1)

Indiana University School of Public Health; 🇺🇸 Bloomington, Indiana, United States