The Effect of Intermittent Fasting on Acute Subconcussive Head Impacts
Condition: Sports Injury; Intermittent Fasting
MeSH terms: Athletic Injuries
Study type: Interventional

Summary: 
      The purpose of this study is to examine the effect of intermittent fasting on the acute
      neural responses to subconcussive head impacts. The study is designed to identify the effects
      of 20 controlled soccer headings in college-aged soccer players in one of four groups
      (fasted, pre-fasted, post-fasted, or control) through the use of neural-injury blood
      biomarkers, magnetic resonance spectroscopy, functional, and diffusion MRI, and ocular-motor
      function across 4 acute time points. The central hypothesis is that the neuronal structural,
      physiological, and functional impairments from the subconussive head impacts will be lessened
      by intermittent fasting either before or after the soccer headings. The neural-injury blood
      biomarkers neurofilament light (NfL), glial fibrillary acidic protein (GFAP), Ubiquitin
      C-Terminal Hydrolase L1 (UCH-L1), and Tau will be measured in serum, with the hypothesis that
      fasting prior to the 20 soccer headings will result in a decreased heightened response
      compared to the post-heading fasted group and the controls. It is also hypothesized that
      repetitive subconcussive head impacts will impair neurocognitive function, as measured by
      regional changes in fMRI activation during a working memory task in the fasted groups. Twenty
      headings will significantly alter fMRI activation in the fasted groups from baseline. This
      impairment will not be observed in the control group. White matter microstructure will be
      measured by diffusion imaging metrics, with the hypothesis that 20 soccer headings will
      significantly disrupt microstructure in the fasted groups compared to baseline, but not in
      the control group. The study will also assess neuro-opthalmologic function as measured by the
      King-Devick test (KDT) and oculomotor function as measured by near-point-of-convergence (NPC)
      in response to subconcussive head impacts. The hypothesis is that NPC performance will be
      significantly impaired for longer than 24 hours in all the groups, but this impairment will
      be greater in the control group, and that the learning curve and expected improvement of KDT
      will be significantly blunted in both groups, with a display worsening in the control group.
    

Detailed description: 
      The researchers will use a randomized controlled trial design and recruit participants on a
      first-come, first-serve basis for the study. The four groups are; 8 day fast, 5 day
      pre-heading fast, 3 day post-heading fast, and control.

      The study consists of 4 data collection time points in an 8-day period. The four data
      collection sessions will last approximately 2 hours. This study design will enable the
      researchers to test outcome measures over subacute and acute phases.

        -  On day 0. the 1st test session takes place immediately prior to the 8-day period.

        -  On day 4, the 2nd test session takes place right before the soccer heading.

        -  Participants will perform the soccer headers.

        -  On day 5, the 3rd test session takes place 24 hours after the soccer heading.

        -  On day 7, the 4th test session takes place 72 hours after the soccer heading.

      When written informed consent is obtained, the researchers will use a self-reported health
      questionnaire to obtain demographic information. The information includes age, sex,
      race/ethnicity, years of soccer playing and heading experience, number and age of previous
      concussions, sleep habits, menstrual cycle, and diet history 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.

      Soccer Heading:

      A standardized and reliable soccer heading protocol will be used for the experiment. A
      triaxial accelerometer and gyroscope (Triax Technologies) embedded in a head-band pocket and
      positioned back of the head 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 across both groups. 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 game. Participants will stand approximately 40ft away from the machine to
      perform soccer ball headings. An average linear head acceleration from a header sits around
      20 g, while regular corner or goal kicks (~50mph) yield accelerations above 50 g.
      Participants in all groups will perform 20 headers with 1 header per 30 seconds.

      Questionnaires:

      The researchers will also (1) assess depression, anxiety, stress and panic symptoms using the
      PHQ-9, GAD-7, and the Daily Stress Inventory; (2) alcohol use disorder using AUDIT; (3)
      cannabis use disorder using CUDIT; (4) mood states using POMS; and (5) concussion symptoms
      using SCAT.

      Biological Impedance Assessment:

      Body weight measures will be taken at each visit using a Bioelectrical Impedance Assessment
      (BIA, Tanita Corporation of America, Arlington Heights, IL). This is a method for estimating
      body composition, in particular body fat, muscle mass, and total body water composition. BIA
      uses a weak electric current flow through the body and the voltage is measured to calculate
      impedance (resistance) of the body.

      NPC and KDT:

      During each test session, various assessments will be conducted on each participant. First,
      ocular assessments consisting of near point of convergence (NPC) and the King-Devick Test
      (KDT) will be used to assessed ocular-motor function and neuro-ophthalmologic function,
      respectively. The NPC measures the closest point to which one can maintain convergence while
      focusing on an object before double vision occurs. Assessment will be repeated twice, and
      mean NPC scores will be used for statistical analyses. After they have finished NPC,
      participants will complete the KDT. The KDT assesses neuro-ophthalmologic function due to
      it's design of saccadic eye movements coupled with multiple facets of brain functions such as
      attention, language, and concentration. It will be administrated on a hand- held tablet.
      Participants will be given one trial "demonstration" card to practice the task. Following the
      demonstration card, participants will tap through 3 test cards. Participants will be asked to
      read aloud, left to right and top to bottom, a series of numbers on the test cards as fast
      and as accurate as they can while refraining from using his/her fingers as a reading guide.
      The 3 test cards progress in difficulty (i.e. guideline disappearance, numbers become more
      dense). The KDT records the total time, in seconds, participants spent to complete the task
      (all 3 test cards). Accuracy will be recorded by a lab personnel member who will stand behind
      the participant and record any errors (incorrect number, missed number, etc.) made during the
      testing.

      Blood Biomarkers:

      Antecubital vein blood draws will be performed each test session to help determine serum
      biomarker concentrations. A trained phlebotomist will thoroughly clean the inner elbow
      surface with an alcohol swab and draw 7 ml of whole blood into sterile Vacutainer tubes with
      21G butterfly needle. After the blood draw, the participant will use gauze to maintain direct
      pressure and a bandage will be provided. Plasma will be assessed by the 4-plex Simoa assay
      platform (Quanterix), which is a magnetic bead-based ELISA that allows detection of
      biomarkers in femtomolar concentrations.

      MRI Techniques:

      Once completing the MRI screening procedure, participants will undergo the following
      standardized MRI protocols.

      Diffusion tensor imaging (DTI) is the most widely used technique to study the microstructural
      integrity of white matter in vivo. DTI provides simple markers, such as mean diffusivity (MD)
      and fractional anisotropy (FA), that have been used to reflect microstructural tissue change
      during aging, neurological disorders, and traumatic brain injury (i.e., concussion). However,
      despite their sensitivity, MD and FA represent cellular diffusivity estimated by basic
      statistical descriptions that do not directly correspond to biophysiological parameters of
      the neural cellular integrity. DTI assumes Gaussian diffusion within a single microstructural
      compartment and thus has proven non-specific to axonal structural damage. To address this
      limitation, neurite orientation dispersion and density imaging (NODDI) has been characterized
      to assess microstructural integrity of axons using a non-Gaussian model with multiple
      compartments. NODDI allows researchers to measure axonal density within white matter,
      orientation of axonal dispersion, and free water diffusion. The combined approach using NODDI
      and DTI will uncover greater depth of progressive axonal degeneration in response to
      repetitive subconcussive head impacts.

      Magnetic Resonance Spectroscopy data will be collected using a single-voxel PRESS (Point
      RESolved Spectroscopy) sequence. The researchers primary region of interest (ROI) for MRS
      analysis is the dorsolateral prefrontal cortex (DLPFC). This region plays a vital role in
      regulating memory, attention, emotion/behavior, and autonomic motor function, and previous
      studies have shown altered neurometabolic levels in this region after concussive and
      subconcussive injuries. The MRS voxel with a dimension of 15x20x25mm3 will be positioned in
      the DLPFC using the T1-weighted image as a reference. There will also be a MRS scan collected
      gathering information on the whole brain to compare to the single voxel scan of the DLPFC.

      N-Back Task: The n-back task will be used to assess verbal (letters) memory. For the verbal
      n-back tasks, while in the scanner, participants will be presented a series of letters, with
      letters being displayed on the screen one at a time. Participants will be instructed to
      answer whether the target letter is the same or different from the letter presented, if it
      the presented target is the same or different from the letter presented 1-back or 2-back
      letters prior. If the target letter is the same, participants will be instructed to press the
      index button of the controller in their left hand and if the letter is different,
      participants will be instructed to press the index button of the controller in their right
      hand. The n-back task has a total duration of about 7 minutes.
    

Intervention name(s): Soccer Heading; Intermittent Fasting
Intervention type(s): Other; Other
Intervention description(s): 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.; The purpose of this study is to examine the effect of intermittent fasting on the acute neural responses to subconcussive head impacts. The study is designed to identify the effects of 20 controlled soccer headings in college-aged soccer players in one of four groups (fasted, pre-fasted, post-fasted, or control) through the use of neural-injury blood biomarkers, magnetic resonance spectroscopy, functional, and diffusion MRI, and ocular-motor function across 4 acute time points. Participants will be randomly designed to one of the four groups which consist of an 8 day fast, 5 day fast, 3 day fast, or the non-fasted control group.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Soccer Heading; Subconcussive Head Impacts; Intermittent Fasting