Effects of Subconcussive Head Impacts on Neural Integrity and Function in ADHD: a Case-control Intervention
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Acute change in axonal microstructure from pre to 2 hour post-heading.
研究概览
简要总结
The purpose of this study is to examine the acute neural responses to subconcussive head impacts in individuals with Attention-deficit/hyperactivity disorder (ADHD). The study is designed to identify the effects of 10 controlled soccer headings in college-aged soccer players diagnosed with ADHD and without ADHD, through the use of neural-injury blood biomarkers, functional and diffusion MRI, and ocular-motor function across three acute timepoints. The central hypothesis is that neuronal structural, physiological, and functional impairments from subconcussive head impacts will be amplified by ADHD. The neural-injury blood biomarkers neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCHL-1), and Tau will be measured in plasma, with the hypothesis that 10 soccer headings will significantly increase plasma NF-L levels in both groups at 24h post-heading compared to baseline, but this increase will be higher in the ADHD group; plasma UCH-L1, GFAP, and Tau levels will increase significantly after 10 headings in the ADHD group at 2h and 24h post-heading, but levels in the non-ADHD group will remain consistent throughout the time points. It is also hypothesized that repetitive subconcussive head impacts will impair neurocognitive function, as measured by regional changes in fMRI activation during working memory and attention-based tasks, in the ADHD group. Ten headings will significantly alter fMRI activation in the ADHD group from baseline. This impairment will not be observed in the non-ADHD group, rather the non-ADHD group will show consistent fMRI activation even after 10 headings. White matter microstructure will be measured by diffusion imaging metrics, with the hypothesis that 10 soccer headings will significantly disrupt microstructure in the ADHD group compared to baseline, but not in the non-ADHD group. The study will also assess neuro-ophthalmologic function as measured by the King-Devick test (KDT) and oculomotor function as measured by the near-point-of-convergence (NPC) in response to subconcussive head impacts. The hypothesis is that NPC performance will be significantly impaired and persist for longer than 24 hours in both groups, but this impairment will be greater in the ADHD group, and that the learning curve and expected improvement of KDT will be significantly blunted in both groups, with a display of worsening in the ADHD group.
详细描述
We will recruit participants on a first-come, first-served basis for the ADHD group. We will select age- and sex-matched controls (e.g., matched to 1st, 3rd, 5th, and 7th ADHD participants since this is 1:2 frequency-matched sampling) for the non-ADHD group. We propose to include a total of 60 participants in the study (ADHD n= 40, non-ADHD n=20).
The study consists of 3 data collection time points in a 2-day period. The 1st day will last approximately 4.75 hours and 2nd day will last approximately 1.5 hours. This study design will enable to test outcome measures over 2 acute phases.
- The 1st test session takes place right before the soccer heading intervention
- Participants will perform the soccer heading intervention
- The 2nd test session takes place 2 hours after the soccer heading intervention
- The 3rd test session takes place approximately 24 hours after the intervention
When written informed consent is obtained, we will use a self-reported health questionnaire to obtain demographic information. The information includes age, sex, BMI, race/ethnicity, years of soccer playing and heading experience, number and age of previous concussions, and sleep habits, as well as assessment of other neurological conditions to screen participants' eligibility. Participants who meet the inclusion criteria and are free of exclusionary factors will advance to the testing procedures. From 3 days before the study until the 24h post-heading time point, participants will be instructed to (1) take ADHD medication (for the ADHD Cohort), (2) refrain from consuming alcohol and recreational drugs, and (3) refrain from activities that involve head impacts.
Soccer Heading Intervention:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
The investigator who administers the semi-structured diagnostic interview for both groups using the Adult ADHD Investigator Symptom Rating Scale (AISRS), which is a robust, valid efficacy measure of ADHD symptoms in adult patients will be blinded to the study participants' diagnosis status. Additionally, the statistician will be blinded from group assignment. These processes will ensure single blind method.
入排标准
- 年龄范围
- 18 Years 至 26 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For ADHD Cohort
- •Aged between 18 and 26 years at the start of the study
- •Providing documentation of ADHD being clinically diagnosed by a psychologist, psychiatrist, or a neurologist 3) Taking their prescribed ADHD medication >5 days a week
- •Currently playing soccer (i.e., intercollegiate, intramural, club) 5) At least 5 years of soccer heading experience
- •For non-ADHD Cohort
- •Aged between 18 and 26 years at the start of the study
- •Absence of prior or current clinical diagnoses of ADHD
- •Absence of prior or current history of taking ADHD medication 4) Currently playing soccer (i.e., intercollegiate, intramural, club) 5) At least 5 years of soccer heading experience
排除标准
- •For both ADHD and non-ADHD Cohorts
- •Any head or neck injury in the year before the start of the study
- •Current use of medications that trigger drowsiness
- •Any history of neurological disorders and learning disability other than ADHD
- •Metal implants in the head
- •Implanted electro/magnetic devices (e.g. orthodontic braces, pacemakers, aneurysm clips)
研究组 & 干预措施
ADHD diagnosis and subconcussive head impacts
ADHD Group: Individuals clinically diagnosed with ADHD, currently taking his/her prescribed ADHD medication.
Device: Soccer Heading Soccer Heading: Subjects stood approximately 40 feet away from a JUGS soccer ball launcher and participated in 20 consecutive soccer headings, separated by one minute intervals.
干预措施: Soccer Heading (Other)
No history or current diagnosis of ADHD and subconcussive head impacts
Non-ADHD Group: Individuals with no current or prior diagnosis of ADHD.
Device: Soccer Heading Soccer Heading: Subjects stood approximately 40 feet away from a JUGS soccer ball launcher and participated in 20 consecutive soccer headings, separated by one minute intervals.
干预措施: Soccer Heading (Other)
结局指标
主要结局
Acute change in axonal microstructure from pre to 2 hour post-heading.
时间窗: MRI procedures will be performed at pre and 2 hour post-heading
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with an eight channel phased array head radiofrequency coil will be used to assess changes in diffusion metrics. Whole-brain Diffusion tensor imaging (DTI) will be performed with a multi-slice single-shot spin echo echoplanar pulse sequence (echo time \[TE\] = 81 ms; repetition time \[TR\] = 9 s) using 64 diffusion-encoding directions, isotopically distributed over the surface of a sphere with electrostatic repulsion. Neurite orientation, dispersion and density imaging (NODDI) metrics will be used in addition to DTI to assess axonal density within white matter, orientation of axonal dispersion, and free water diffusion.
Acute change in regional fMRI activation during memory and attention tasks from pre to 2 hour post-heading
时间窗: fMRI procedures will be performed at pre and 2 hour post-heading
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with an eight channel phased array head radiofrequency coil will be used to collect fMRI images while attention and working memory tasks are administered. The task based fMRI protocol will consist of N-Back tasks to assess visual and verbal working memory, Flanker task to assess attention, and a function Resting State task.
Acute change in brain-derived blood biomarkers from pre to 2 hour post-heading
时间窗: Blood samples will be collected at pre- and 2 hour post-heading
Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Serum samples will be aliquoted and stored at -80 degree celsius until analysis. Serum samples will be assayed for neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), tau, and Ubiquitin C-terminal Hydrolase 1 (UCH-L1). All expression levels in pg/mL.
Acute change in axonal microstructure from pre to 24 hour post-heading.
时间窗: MRI procedures will be performed at pre and 24 hour post-heading
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with an eight channel phased array head radiofrequency coil will be used to assess changes in diffusion metrics. Whole-brain Diffusion tensor imaging (DTI) will be performed with a multi-slice single-shot spin echo echoplanar pulse sequence (echo time \[TE\] = 81 ms; repetition time \[TR\] = 9 s) using 64 diffusion-encoding directions, isotopically distributed over the surface of a sphere with electrostatic repulsion. Neurite orientation, dispersion and density imaging (NODDI) metrics will be used in addition to DTI to assess axonal density within white matter, orientation of axonal dispersion, and free water diffusion.
Acute change in brain-derived blood biomarkers from pre to 24 hour post-heading
时间窗: Blood samples will be collected at pre- and 24 hour post-heading
Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Serum samples will be aliquoted and stored at -80 degree celsius until analysis. Serum samples will be assayed for neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), tau, and Ubiquitin C-terminal Hydrolase 1 (UCH-L1). All expression levels in pg/mL.
Acute change in regional fMRI activation during memory and attention tasks from pre to 24 hour post-heading
时间窗: fMRI procedures will be performed at pre and 2 hour post-heading
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with an eight channel phased array head radiofrequency coil will be used to collect fMRI images while attention and working memory tasks are administered. The task based fMRI protocol will consist of N-Back tasks to assess visual and verbal working memory, Flanker task to assess attention, and a function Resting State task.
次要结局
- Acute change in ocular-motor function from pre to 24 hour post-heading(Ocular-motor function will be assessed at pre- and 24 hour post-heading)
- Acute change in ocular-motor function from pre to 2 hour post-heading(Ocular-motor function will be assessed at pre- and 2 hour post-heading)
研究者
Keisuke Kawata
Assistant Professor Kinesiology
Indiana University