Omega-3 Fatty Acids and Subconcussive Head Impacts

NCT ID: NCT06736925

Last Updated: 2025-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-28

Study Completion Date

2029-05-31

Brief Summary

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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.

Detailed Description

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The purpose of the proposed study is to determine whether, and to what extent, supplementation with omega-3 fatty acids \[docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)\] can maintain or promote neural wellbeing against repetitive subconcussive head impacts. This study will also characterize what aspects of brain cellular and physiologic resiliencies are enhanced by supplementation in adult soccer players (aged 18-30 years old). A sub-cohort of participants who meet criteria for ADHD diagnosis will be part of exploratory analysises.

Conditions

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Subconcussive Head Impact Omega-3 Fatty Acids

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
Several co-investigators and undergraduate researchers will remain masked throughout the trial.

Study Groups

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Placebo: Organic soybean oil pills

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.

Group Type PLACEBO_COMPARATOR

Organic soybean oil

Intervention Type 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.

Soccer Heading Model

Intervention Type 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)

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 \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Group Type ACTIVE_COMPARATOR

Omega-3 Fatty Acids (EPA plus DHA)

Intervention Type 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 \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Soccer Heading Model

Intervention Type 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.

Interventions

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Omega-3 Fatty Acids (EPA plus DHA)

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 \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].

Intervention Type DIETARY_SUPPLEMENT

Organic soybean oil

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.

Intervention Type DIETARY_SUPPLEMENT

Soccer Heading Model

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role lead

Responsible Party

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Keisuke Kawata

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Indiana University School of Public Health

Bloomington, Indiana, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kei Kawata

Role: CONTACT

812-855-5244

Facility Contacts

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Kei Kawata

Role: primary

812-855-5244

References

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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.

Reference Type BACKGROUND
PMID: 23483891 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28181857 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24806476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26700106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29807487 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28404801 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29966462 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33280186 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33414022 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34338724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31633894 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40273177 (View on PubMed)

Other Identifiers

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R01NS137276

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21334

Identifier Type: -

Identifier Source: org_study_id

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