Sports InjuryNCT05236127
The Effect of Intermittent Fasting on Acute Subconcussive Head Impacts
A study testing Soccer Heading and Intermittent Fasting in people with Sports Injury and Intermittent Fasting, run by Indiana University at 1 site in United States.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Sports Injury, Intermittent Fasting
- What is being tested?
- Soccer Heading and Intermittent Fasting
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2022to 31 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-30 years of age
- At least three years of soccer heading experience
Who cannot join
- Diabetes
- Any current intermittent fasting or in the last 3-6 months
- Any head or eye injury 12 months prior to the study
- Any neurological disorders (e.g., seizures, closed head injuries with prolonged loss of consciousness (> 15 minutes), history of stroke, spinal cord/surgery)
- History of vestibular, ocular, or vision dysfunction
- Any injury that would prohibit the performance of soccer headings
Show all 11Show fewer
- A history of eating disorder
- Any brain implants or recent surgeries with metal implants that prohibit undergoing an MRI
- Currently taking any medications affecting appetite
- Pregnant
- HIV
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University School of Public Health
Bloomington, Indiana, 47405
About this study
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.
Read the 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.
- Conditions
- Sports Injury, Intermittent Fasting
- Being tested
- Soccer Heading, Intermittent Fasting
- Keywords
- Soccer Heading, Subconcussive Head Impacts, Intermittent Fasting
- Medical subject headings
- Athletic Injuries, Intermittent Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Soccer HeadingOther
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.
Intermittent FastingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Fasted | Experimental | Fasted Group: Individuals randomly assigned to undergo a 20 hour fast with a four hour eating window for the entire 8-day period of the study. Receives: Other: Intermittent Fasting |
| Pre-heading fasted | Experimental | Pre-Heading Fasted Group: Individuals randomly assigned to undergo a 20 hour fast with a 4 hour eating window for a 5-day period prior to the soccer heading. Receives: Other: Intermittent Fasting |
| Post-heading fasted | Experimental | Post-Heading Fasted Group: Individuals randomly assigned to undergo a 20 hour fast with a four hour eating window for a 3-day period following the soccer heading. Receives: Other: Intermittent Fasting |
| Control | Experimental | Control Group: Individuals randomly assigned to eat per usual over the course of the entire 8-day study period. Receives: Other: Intermittent Fasting |
| Subconcussive Head Impact | Active comparator | All four groups undergo the same soccer heading model as described below.
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 30 second intervals. Receives: Other: Soccer Heading |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in brain-derived blood biomarkers from day 4 to day 5 and group differences
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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Measured: Blood samples will be collected at day 4 (prior to heading) and day 5 (24 hours post-heading).
Change in brain-derived blood biomarkers from day 4 to day 7 and group differences
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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Measured: Blood samples will be collected at day 4 (prior to heading) and day 7 (72 hours post heading).
Change in regional fMRI activation during the memory task from day 4 to day 5 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect fMRI images while a working memory task is administered.
The task based fMRI protocol consists of N-back verbal working memory and a resting state task.
Measured: fMRI procedures will be performed on day 4 (prior to heading) and day 5 (24 hours post-heading)
Change in regional fMRI activation during the memory task from day 4 to day 7 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect fMRI images while a working memory task is administered.
The task based fMRI protocol consists of N-back verbal working memory and a resting state task.
Measured: fMRI procedures will be performed on day 4 (prior to heading) and day 7 (72 hours post-heading)
Change in regional resting state functional connectivity from day 4 to day 5 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect resting state functional connectivity.
Measured: fMRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
Change in regional resting state functional connectivity from day 4 to day 7 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect resting state functional connectivity.
Measured: fMRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in axonal microstructure from day 4 to day 5 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 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.
Measured: MRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
Change in axonal microstructure from day 4 to day 7 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 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.
Measured: MRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in a panel of metabolites from day 4 to day 5 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to assess changes in neurometabolic metrics. The metabolic panel includes the following: N-Acetylaspartate (NAA), Glutamine/Glutamate (Glx), Myo-Inositol (mI), Choline (Cho), and Creatine (Cr).
Measured: MRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
Change in a panel of metabolites from day 4 to day 7 and group differences
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to assess changes in neurometabolic metrics. The metabolic panel includes the following: N-Acetylaspartate (NAA), Glutamine/Glutamate (Glx), Myo-Inositol (mI), Choline (Cho), and Creatine (Cr).
Measured: MRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
Secondary outcomes (7)
Change in near point of convergence from day 0 to day 4 and group differences
Participants will undergo a brief test of near-point of convergence
Measured: Near point of convergence will be assessed at day 0 and day 4 (prior to heading).
Change in near point of convergence from day 4 to day 7 and group differences
Participants will undergo a brief test of near-point of convergence
Measured: Near point of convergence will be assessed at day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in King Devick performance from day 0 to day 4 and group differences
Participants will undergo the King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing
Measured: King Devick performance will be assessed at day 0 and day 4 (prior to heading)
Change in King Devick performance from day 4 to day 7 and group differences
Participants will undergo the King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing
Measured: King Devick performance will be assessed at day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in brain-derived blood biomarkers from day 0 to day 4 and group differences
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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Measured: Blood samples will be collected at day 0 and day 4 (prior to heading).
Change in brain-derived blood biomarkers from day day 0 to day 5 and group differences
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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Measured: Blood samples will be collected at day 0 and day 5 (24 hours post heading).
Change in brain-derived blood biomarkers from day day 0 to day 7 and group differences
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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Measured: Blood samples will be collected at day 0 and day 7 (72 hours post heading).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2022
- Study start23 Jan 2022
- Primary completion31 Aug 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sports InjuryStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keisuke Kawata, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05236127
- Sponsor's protocol ID
- 13076
- Status last verified
- Sep 2023
- First submitted
- 16 Nov 2021
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All study data will be included in publications.
Publications
Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31.
PubMed 29086496Kawata K, Steinfeldt JA, Huibregtse ME, Nowak MK, Macy JT, Kercher K, Rettke DJ, Shin A, Chen Z, Ejima K, Newman SD, Cheng H. Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study. Front Neurol. 2020 Nov 16;11:581781. doi: 10.3389/fneur.2020.581781. eCollection 2020.
PubMed 33304306Nowak 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.
PubMed 32053162Koerte IK, Lin AP, Muehlmann M, Merugumala S, Liao H, Starr T, Kaufmann D, Mayinger M, Steffinger D, Fisch B, Karch S, Heinen F, Ertl-Wagner B, Reiser M, Stern RA, Zafonte R, Shenton ME. Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion. J Neurotrauma. 2015 Sep 1;32(17):1287-93. doi: 10.1089/neu.2014.3715. Epub 2015 May 14.
PubMed 25843317
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Intermittent Fasting on Acute Subconcussive Head Impacts
- ClinicalTrials.gov ID
- NCT05236127
- Acronym / sponsor ID
- 13076
- Conditions
- Sports Injury, Intermittent Fasting
- Keywords
- Soccer Heading, Subconcussive Head Impacts, Intermittent Fasting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 23 Jan 2022 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 11 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Fasted | Experimental | Other: Intermittent FastingFasted Group: Individuals randomly assigned to undergo a 20 hour fast with a four hour eating window for the entire 8-day period of the study. |
| Pre-heading fasted | Experimental | Other: Intermittent FastingPre-Heading Fasted Group: Individuals randomly assigned to undergo a 20 hour fast with a 4 hour eating window for a 5-day period prior to the soccer heading. |
| Post-heading fasted | Experimental | Other: Intermittent FastingPost-Heading Fasted Group: Individuals randomly assigned to undergo a 20 hour fast with a four hour eating window for a 3-day period following the soccer heading. |
| Control | Experimental | Other: Intermittent FastingControl Group: Individuals randomly assigned to eat per usual over the course of the entire 8-day study period. |
| Subconcussive Head Impact | Active comparator | Other: Soccer HeadingAll four groups undergo the same soccer heading model as described below. 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 30 second intervals. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 18-30 years of age
- At least three years of soccer heading experience
Key exclusion criteria (11 listed)
- Diabetes
- Any current intermittent fasting or in the last 3-6 months
- Any head or eye injury 12 months prior to the study
- Any neurological disorders (e.g., seizures, closed head injuries with prolonged loss of consciousness (> 15 minutes), history of stroke, spinal cord/surgery)
- History of vestibular, ocular, or vision dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Soccer HeadingA 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. | Other | Subconcussive Head Impact |
| Intermittent FastingThe 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. | Other | Control, Fasted, Post-heading fasted, Pre-heading fasted |
Primary outcome
Change in brain-derived blood biomarkers from day 4 to day 5 and group differences
Time frame: Blood samples will be collected at day 4 (prior to heading) and day 5 (24 hours 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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Change in brain-derived blood biomarkers from day 4 to day 7 and group differences
Time frame: Blood samples will be collected at day 4 (prior to heading) and day 7 (72 hours 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) and glial fibrillary acidic protein (GFAP). All expression levels in pg/mL.
Change in regional fMRI activation during the memory task from day 4 to day 5 and group differences
Time frame: fMRI procedures will be performed on day 4 (prior to heading) and day 5 (24 hours post-heading)
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect fMRI images while a working memory task is administered. The task based fMRI protocol consists of N-back verbal working memory and a resting state task.
Change in regional fMRI activation during the memory task from day 4 to day 7 and group differences
Time frame: fMRI procedures will be performed on day 4 (prior to heading) and day 7 (72 hours post-heading)
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect fMRI images while a working memory task is administered. The task based fMRI protocol consists of N-back verbal working memory and a resting state task.
Change in regional resting state functional connectivity from day 4 to day 5 and group differences
Time frame: fMRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect resting state functional connectivity.
Change in regional resting state functional connectivity from day 4 to day 7 and group differences
Time frame: fMRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to collect resting state functional connectivity.
Change in axonal microstructure from day 4 to day 5 and group differences
Time frame: MRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 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.
Change in axonal microstructure from day 4 to day 7 and group differences
Time frame: MRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 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.
Change in a panel of metabolites from day 4 to day 5 and group differences
Time frame: MRI procedures will be performed day 4 (prior to heading) and day 5 (24 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to assess changes in neurometabolic metrics. The metabolic panel includes the following: N-Acetylaspartate (NAA), Glutamine/Glutamate (Glx), Myo-Inositol (mI), Choline (Cho), and Creatine (Cr).
Change in a panel of metabolites from day 4 to day 7 and group differences
Time frame: MRI procedures will be performed day 4 (prior to heading) and day 7 (72 hours post-heading).
A standardized MRI protocol acquired on a Siemens TIM Trio scanner, equipped with a 64 channel phased array head radiofrequency coil will be used to assess changes in neurometabolic metrics. The metabolic panel includes the following: N-Acetylaspartate (NAA), Glutamine/Glutamate (Glx), Myo-Inositol (mI), Choline (Cho), and Creatine (Cr).
7 secondary outcomes
Change in near point of convergence from day 0 to day 4 and group differences
Time frame: Near point of convergence will be assessed at day 0 and day 4 (prior to heading).
Change in near point of convergence from day 4 to day 7 and group differences
Time frame: Near point of convergence will be assessed at day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in King Devick performance from day 0 to day 4 and group differences
Time frame: King Devick performance will be assessed at day 0 and day 4 (prior to heading)
Change in King Devick performance from day 4 to day 7 and group differences
Time frame: King Devick performance will be assessed at day 4 (prior to heading) and day 7 (72 hours post-heading).
Change in brain-derived blood biomarkers from day 0 to day 4 and group differences
Time frame: Blood samples will be collected at day 0 and day 4 (prior to heading).
Change in brain-derived blood biomarkers from day day 0 to day 5 and group differences
Time frame: Blood samples will be collected at day 0 and day 5 (24 hours post heading).
Change in brain-derived blood biomarkers from day day 0 to day 7 and group differences
Time frame: Blood samples will be collected at day 0 and day 7 (72 hours post heading).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Background: PubMed 29086496Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31.
- Background: PubMed 33304306Kawata K, Steinfeldt JA, Huibregtse ME, Nowak MK, Macy JT, Kercher K, Rettke DJ, Shin A, Chen Z, Ejima K, Newman SD, Cheng H. Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study. Front Neurol. 2020 Nov 16;11:581781. doi: 10.3389/fneur.2020.581781. eCollection 2020.
- Background: PubMed 32053162Nowak 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.
- Background: PubMed 25843317Koerte IK, Lin AP, Muehlmann M, Merugumala S, Liao H, Starr T, Kaufmann D, Mayinger M, Steffinger D, Fisch B, Karch S, Heinen F, Ertl-Wagner B, Reiser M, Stern RA, Zafonte R, Shenton ME. Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion. J Neurotrauma. 2015 Sep 1;32(17):1287-93. doi: 10.1089/neu.2014.3715. Epub 2015 May 14.
- Individual participant dataSharing planned: No. All study data will be included in publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Soccer Heading and Intermittent Fasting in people with Sports Injury and Intermittent Fasting, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in brain-derived blood biomarkers from day 4 to day 5 and group differences (time frame: Blood samples will be collected at day 4 (prior to heading) and day 5 (24 hours post-heading).). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05236127, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.