The Effect of Intermittent Fasting on Acute Subconcussive Head Impacts

NCT05236127 | Completed DMC

• 1 other identifier: 13076
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sports Injury; Intermittent Fasting

Keywords

Soccer Heading; Subconcussive Head Impacts; Intermittent Fasting

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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).

  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

  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

  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

  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

  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 at day 0 and day 4 (prior to heading).

Study Arms (5)

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.

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.

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.

Other: Intermittent Fasting

Control

EXPERIMENTAL

Control Group: Individuals randomly assigned to eat per usual over the course of the entire 8-day study period.

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.

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.

Subconcussive Head Impact

Intermittent Fasting OTHER

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.

Control; Fasted; Post-heading fasted; Pre-heading fasted

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years of age
• At least three years of soccer heading experience

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University School of Public Health

Bloomington, Indiana, 47405, United States

Location

Related Publications (4)

• 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.

  PMID: 29086496 BACKGROUND

• Kawata 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.

  PMID: 33304306 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

• Koerte 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.

  PMID: 25843317 BACKGROUND

MeSH Terms

Conditions

Athletic Injuries; Intermittent Fasting

Condition Hierarchy (Ancestors)

Wounds and Injuries; Fasting; Feeding Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The primary investigator will be blinded to the study participants' study group status. Additionally, the statistician will be blinded from group assignment.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Kinesiology

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: February 11, 2022
• Study Start: January 23, 2022
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)