Omega-3 Fatty Acids and Subconcussive Head Impacts

NCT06736925 | Recruiting

• 2 other identifiers: 21334R01NS137276
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the proposed double-blind, randomized placebo-controlled trial is to understand how supplementation with fish oil \[docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)\] promote brain health against soccer heading. The study involves taking DHA+EPA or placebo, questionnaires, blood draws, brain imaging, tests to evaluate heart function, and soccer headings.

Conditions

Subconcussive Head Impact; Omega-3 Fatty Acids

Keywords

Subconcussive brain injury; TBI; Soccer heading; Omega-3 fatty acids

Outcome Measures

Primary Outcomes (5)

• Blood Biomarkers

  The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically NF-L (neurofilament light, ), tau (picogram per milliliter), GFAP (glial fibrillary acidic protein; nanograms per milliliter), UCH-L1 (ubiquitin C-terminal hydrolase-L1; picograms per milliliter), and S100B (S100 calcium binding protein B; nanograms per milliliter). The aggregation of all blood biomarkers will provide a comprehensive overview of the biofluid profile of the participant following repetitive head injury.

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Diffusion Tensor Imaging

  DTI will be used to derive mean diffusivity (MD; square millimeters per second) and fractional anisotropy (FA; a unitless value that ranges from 0 to 1, 0 = Isotropic, 1= Anisotropic) as indicators joint of axonal integrity (axonal microstructure) and connectivity of white matter tracts by measuring how water molecules move through brain tissues .

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Sympathetic Reactivity

  Sympathetic Reactivity will be measured by the Cold Pressor Test (CPT). CPT is a general assessment of the ability of the sympathetic nervous system to become activated. The main metric will be changes in mean arterial pressure (MAP) following soccer headings. This test will be performed by submerging a participants hand into cold water for 2 minutes while autonomic and hemodynamic variables are recorded. At each data collection, participants will be instrumented for the measurement of heart rate (electrocardiogram) and continuous blood pressure. Participants will rest quietly for \~10 minutes before the CPT begins. The test takes 2 minutes.

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Near Point Convergence

  Using the accommodative ruler, a target (14-point letter) will be moved toward the eyes at a rate of 1-2 cm/s. NPC will be recorded when participants report diplopia has occurred, or the tester observes eye misalignment. The assessment will be repeated twice, and the mean near point convergence value will be used for analyses.

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• King-Devick test

  The King-Devick test (KDT) consists of a total of 145 saccades while rapidly reading numbers aloud to complete the test. The KDT will be administered on a tablet. The total time (in seconds) will be used for analysis.

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

Secondary Outcomes (8)

• Neurite Orientation Dispersion and Density Imaging (NODDI)

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Resting-state functional connectivity

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Cardiovagal baroreflex sensitivity

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Heart rate variability

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

• Cognition

  Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session

Other Outcomes (2)

• Genetic markers

  Baseline

• ADHD

  Baseline

Study Arms (2)

Placebo: Organic soybean oil pills

PLACEBO COMPARATOR

We will use organic soybean oil pills ) as a placebo condition for the DHA+EPA group. One capsule contains 485 mg of organic soybean oil, including negligible amounts of DHA (1.1 mg), EPA (1.7 mg), and vitamin E (10 mg). Participants will ingest 5 capsules daily. Soybean oil is one of the most widely used vegetable oils in the world. Soybean oil contains polyunsaturated fats and 18-carbon omega-3 FA (total omega-3 FA of 73.9 mg per capsule), but very low levels of DHA and EPA, which makes it an excellent placebo counterpart when evaluating the effects of DHA/EPA. The placebo capsule's shelf life, composition, shape, size as the DHA+EPA active comparator.

Dietary Supplement: Organic soybean oil; Other: Soccer Heading Model

Omega-3 Fatty Acids (EPA plus DHA)

ACTIVE COMPARATOR

DHA+EPA capsules contain purified deep-sea fish oil, made from 100% wild-caught sardines and anchovies with a 3-year shelf life. The capsule shell is made from bovine limed bone with a size of 20 oblongs. Each soft gel capsule contains 480 mg of DHA, 205 mg of EPA, 145 mg of other omega-3 FA, and 10 mg of vitamin E. Participants in the DHA+EPA group will ingest 5 capsules daily \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Dietary Supplement: Omega-3 Fatty Acids (EPA plus DHA); Other: Soccer Heading Model

Interventions

Omega-3 Fatty Acids (EPA plus DHA) DIETARY_SUPPLEMENT

DHA+EPA capsules contain purified deep-sea fish oil, made from 100% wild-caught sardines and anchovies with a 3-year shelf life. The capsule shell is made from bovine limed bone with a size of 20 oblongs. Each soft gel capsule contains 480 mg of DHA, 205 mg of EPA, 145 mg of other omega-3 FA, and 10 mg of vitamin E. Participants in the DHA+EPA group will ingest 5 capsules daily \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Omega-3 Fatty Acids (EPA plus DHA)

Organic soybean oil DIETARY_SUPPLEMENT

We will use organic soybean oil pills ) as a placebo condition for the DHA+EPA group. One capsule contains 485 mg of organic soybean oil, including negligible amounts of DHA (1.1 mg), EPA (1.7 mg), and vitamin E (10 mg). Participants will ingest 5 capsules daily. Soybean oil is one of the most widely used vegetable oils in the world. Soybean oil contains polyunsaturated fats and 18-carbon omega-3 FA (total omega-3 FA of 73.9 mg per capsule), but very low levels of DHA and EPA, which makes it an excellent placebo counterpart when evaluating the effects of DHA/EPA. The placebo capsule's shelf life, composition, shape, size as the DHA+EPA active comparator.

Placebo: Organic soybean oil pills

Soccer Heading Model OTHER

A standardized and reliable soccer heading protocol will be used for the experiment. A triaxial accelerometer (G-force tracker) 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 30 mph. 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 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.

Omega-3 Fatty Acids (EPA plus DHA); Placebo: Organic soybean oil pills

Eligibility Criteria

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

You may qualify if:

• Between age 18-30
• Current or former soccer player
• At least 5 years of soccer heading experience
• Have internet access
• Willing to commit to avoid any sport activity that purposefully uses one's head to maneuver during the study period (American football, ice-hockey, rugby, wrestling, and soccer heading).

You may not qualify if:

• Any head or neck injury within 6 months before the study
• Implanted metal/magnetic devices (e.g., orthodontic braces
• Diagnosed autonomic or cardiovascular diseases (e.g., hypertension)
• Consuming oily fish (2 servings or more/month: salmon, bluefin, swordfish, anchovies)
• Allergy to fish or shellfish
• Consuming omega-3 FA supplements including plant-based (e.g., flaxseed) in the past 3 months.
• Pregnancy

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Indiana University School of Public Health

Bloomington, Indiana, 47405, United States

RECRUITING

Related Publications (12)

• Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D. Consequences of repeated blood-brain barrier disruption in football players. PLoS One. 2013;8(3):e56805. doi: 10.1371/journal.pone.0056805. Epub 2013 Mar 6.

  PMID: 23483891 BACKGROUND

• Kawata K, Rubin LH, Takahagi M, Lee JH, Sim T, Szwanki V, Bellamy A, Tierney R, Langford D. Subconcussive Impact-Dependent Increase in Plasma S100beta Levels in Collegiate Football Players. J Neurotrauma. 2017 Jul 15;34(14):2254-2260. doi: 10.1089/neu.2016.4786. Epub 2017 Apr 27.

  PMID: 28181857 BACKGROUND

• Puvenna V, Brennan C, Shaw G, Yang C, Marchi N, Bazarian JJ, Merchant-Borna K, Janigro D. Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits. PLoS One. 2014 May 7;9(5):e96296. doi: 10.1371/journal.pone.0096296. eCollection 2014.

  PMID: 24806476 BACKGROUND

• Oliver JM, Jones MT, Kirk KM, Gable DA, Repshas JT, Johnson TA, Andreasson U, Norgren N, Blennow K, Zetterberg H. Serum Neurofilament Light in American Football Athletes over the Course of a Season. J Neurotrauma. 2016 Oct 1;33(19):1784-1789. doi: 10.1089/neu.2015.4295. Epub 2016 Mar 16.

  PMID: 26700106 BACKGROUND

• Oliver JM, Anzalone AJ, Stone JD, Turner SM, Blueitt D, Garrison JC, Askow AT, Luedke JA, Jagim AR. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29;130(5):1655-1662. doi: 10.3171/2017.12.JNS172035. Print 2019 May 1.

  PMID: 29807487 BACKGROUND

• Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology. 2017 May 9;88(19):1788-1794. doi: 10.1212/WNL.0000000000003912. Epub 2017 Apr 12.

  PMID: 28404801 BACKGROUND

• Joseph JR, Swallow JS, Willsey K, Lapointe AP, Khalatbari S, Korley FK, Oppenlander ME, Park P, Szerlip NJ, Broglio SP. Elevated markers of brain injury as a result of clinically asymptomatic high-acceleration head impacts in high-school football athletes. J Neurosurg. 2018 Jul 3;130(5):1642-1648. doi: 10.3171/2017.12.JNS172386. Print 2019 May 1.

  PMID: 29966462 BACKGROUND

• Tierney GJ, Higgins B. The incidence and mechanism of heading in European professional football players over three seasons. Scand J Med Sci Sports. 2021 Apr;31(4):875-883. doi: 10.1111/sms.13900. Epub 2021 Jan 18.

  PMID: 33280186 BACKGROUND

• Peek K, Vella T, Meyer T, Beaudouin F, McKay M. The incidence and characteristics of purposeful heading in male and female youth football (soccer) within Australia. J Sci Med Sport. 2021 Jun;24(6):603-608. doi: 10.1016/j.jsams.2020.12.010. Epub 2020 Dec 26.

  PMID: 33414022 BACKGROUND

• Russell ER, Mackay DF, Stewart K, MacLean JA, Pell JP, Stewart W. Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players. JAMA Neurol. 2021 Sep 1;78(9):1057-1063. doi: 10.1001/jamaneurol.2021.2403.

  PMID: 34338724 BACKGROUND

• Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. N Engl J Med. 2019 Nov 7;381(19):1801-1808. doi: 10.1056/NEJMoa1908483. Epub 2019 Oct 21.

  PMID: 31633894 BACKGROUND

• Beauregard LH, Bazarian JJ, Johnson BD, Cheng H, Ellis G, Kronenberger W, Calder PC, Chen Z, Silveyra P, Quinn PD, Newman SD, Mickleborough TD, Kawata K. Investigating omega-3 fatty acids' neuroprotective effects in repetitive subconcussive neural injury: Study protocol for a randomized placebo-controlled trial. PLoS One. 2025 Apr 24;20(4):e0321808. doi: 10.1371/journal.pone.0321808. eCollection 2025.

  PMID: 40273177 DERIVED

MeSH Terms

Interventions

Fatty Acids, Omega-3

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Central Study Contacts

Kei Kawata

CONTACT

812-855-5244; kkawata@indiana.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Several co-investigators and undergraduate researchers will remain masked throughout the trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: One group will be randomly assigned to take DHA+EPA, while the other group will be randomly assigned to take the placebo, organic soybean oil. Both groups will received identical stimuli of 20 soccer headings per session for a total of 2 sessions.

Study Record Dates

• First Submitted: October 22, 2024
• First Posted: December 17, 2024
• Study Start: February 28, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)