Defining the Role of Repetitive Head Impact Time Intervals in Mitigating Subconcussive Neural Injury
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Quantitative Electroencephalography (qEEG)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The blood biomarker experimentalist and lead statistician will be masked throughout the trial.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Short Interval - heading
Participants in the heading group will undergo 16 soccer headings, twice per week, with 24 hours in between each session.
干预措施: Short Interval (Other)
Short Interval - heading
Participants in the heading group will undergo 16 soccer headings, twice per week, with 24 hours in between each session.
干预措施: BrainScope qEEG (Device)
Long Interval - heading
Participants in the heading group will undergo 16 soccer headings, twice per week, with 72 hours in between each session.
干预措施: Long Interval (Other)
Long Interval - heading
Participants in the heading group will undergo 16 soccer headings, twice per week, with 72 hours in between each session.
干预措施: BrainScope qEEG (Device)
Short Interval - kicking
Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 24 hours in between each session.
干预措施: Short Interval (Other)
Short Interval - kicking
Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 24 hours in between each session.
干预措施: BrainScope qEEG (Device)
Long Interval - kicking
Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 72 hours in between each session.
干预措施: Long Interval (Other)
Long Interval - kicking
Participants in the kicking-control group will undergo 16 soccer kicking, twice per week, with 72 hours in between each session.
干预措施: BrainScope qEEG (Device)
结局指标
主要结局
Quantitative Electroencephalography (qEEG)
时间窗: 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.
Blood Biomarkers - NfL
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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).
次要结局
- 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)
- Pupillary Size Measurement and Reactivity 5(Baseline, 24 hours following the final heading session, 14 days following the final heading session)
- Pupillary Size Measurement and Reactivity 6(Baseline, 24 hours following the final heading session, 14 days following the final heading session)
- Pupillary Size Measurement and Reactivity7(Baseline, 24 hours following the final heading session, 14 days following the final heading session)
- Near Point of Convergence (NPC)(Baseline, 24 hours following the final heading session, 14 days following the final heading session)
- Choice Reaction Time (CRT)(Baseline, 24 hours following the final heading session, 14 days following the final heading session)
研究者
Keisuke Kawata
Associate Professor
Indiana University