Effects of Subconcussive Head Impacts on Neural Integrity and Function in ADHD

NCT04880304 | Completed DMC

• 1 other identifier: 2007515951
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sport Injury; Attention-deficit/Hyperactivity Disorder

Keywords

Soccer Heading; Subconcussive Head Impacts; Attention-deficit/hyperactivity disorder

Outcome Measures

Primary Outcomes (6)

• Acute change in brain-derived blood biomarkers from pre to 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.

  Blood samples will be collected at pre- and 2 hour post-heading

• Acute change in brain-derived blood biomarkers from pre to 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.

  Blood samples will be collected at pre- and 24 hour post-heading

• Acute change in regional fMRI activation during memory and attention tasks from pre to 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.

  fMRI procedures will be performed at pre and 2 hour post-heading

• Acute change in regional fMRI activation during memory and attention tasks from pre to 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 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.

  fMRI procedures will be performed at pre and 2 hour post-heading

• Acute change in axonal microstructure from pre to 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.

  MRI procedures will be performed at pre and 2 hour post-heading

• Acute change in axonal microstructure from pre to 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.

  MRI procedures will be performed at pre and 24 hour post-heading

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

ADHD diagnosis and subconcussive head impacts

EXPERIMENTAL

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.

Other: Soccer Heading

No history or current diagnosis of ADHD and subconcussive head impacts

EXPERIMENTAL

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.

Other: Soccer Heading

Interventions

Soccer Heading OTHER

A standardized and reliable soccer heading protocol will be used for the experiment. A triaxial accelerometer embedded in a head-band pocket and positioned directly below the external occipital protuberance (inion) to monitor linear and rotational head accelerations. A JUGS soccer machine will be used to simulate a soccer throw-in with a standardized ball speed of 25mph. The ball speed is similar to when soccer players make a long throw-in from the sideline to mid-field. Soccer players frequently perform this maneuver during practice and games. Subjects will stand approximately 40ft away from the machine to perform the heading. Participants perform 20 standing headers with 1 header per 30 seconds. The subjects will be instructed to direct the ball back toward the JUGS soccer machine in the air.

ADHD diagnosis and subconcussive head impacts

Eligibility Criteria

• Age: 18 Years - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Pregnancy
• 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)

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University School of Public Health

Bloomington, Indiana, 47405, United States

Location

Related Publications (5)

• Biederman J, Feinberg L, Chan J, Adeyemo BO, Woodworth KY, Panis W, McGrath N, Bhatnagar S, Spencer TJ, Uchida M, Kenworthy T, Grossman R, Zafonte R, Faraone SV. Mild Traumatic Brain Injury and Attention-Deficit Hyperactivity Disorder in Young Student Athletes. J Nerv Ment Dis. 2015 Nov;203(11):813-9. doi: 10.1097/NMD.0000000000000375.

  PMID: 26461480 BACKGROUND

• Iaccarino MA, Fitzgerald M, Pulli A, Woodworth KY, Spencer TJ, Zafonte R, Biederman J. Sport concussion and attention deficit hyperactivity disorder in student athletes: A cohort study. Neurol Clin Pract. 2018 Oct;8(5):403-411. doi: 10.1212/CPJ.0000000000000525.

  PMID: 30564494 BACKGROUND

• Nowak MK, Bevilacqua ZW, Ejima K, Huibregtse ME, Chen Z, Mickleborough TD, Newman SD, Kawata K. Neuro-Ophthalmologic Response to Repetitive Subconcussive Head Impacts: A Randomized Clinical Trial. JAMA Ophthalmol. 2020 Apr 1;138(4):350-357. doi: 10.1001/jamaophthalmol.2019.6128.

  PMID: 32053162 BACKGROUND

• Wirsching A, Chen Z, Bevilacqua ZW, Huibregtse ME, Kawata K. Association of Acute Increase in Plasma Neurofilament Light with Repetitive Subconcussive Head Impacts: A Pilot Randomized Control Trial. J Neurotrauma. 2019 Feb 15;36(4):548-553. doi: 10.1089/neu.2018.5836. Epub 2018 Sep 4.

  PMID: 30019617 BACKGROUND

• Nowak MK, Kronenberger WG, Rettke D, Ogbeide O, Klemsz LM, Quinn PD, Mickleborough TD, Newman SD, Kawata K. Neuro-ophthalmologic and blood biomarker responses in ADHD following subconcussive head impacts: a case-control trial. Front Psychiatry. 2023 Nov 22;14:1230463. doi: 10.3389/fpsyt.2023.1230463. eCollection 2023.

  PMID: 38076682 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Kinesiology

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 10, 2021
• Study Start: March 15, 2021
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)