Omega-3 Fatty Acids and Subconcussive Head Impacts

Not Applicable

Recruiting

• Conditions: Subconcussive Head Impact; Omega-3 Fatty Acids

• Registration Number: NCT06736925
• Lead Sponsor: Indiana University

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-10-22
• Study First Submitted QC: 2024-12-11
• Study First Posted: 2024-12-17
• Study Start: 2025-02-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-05
• Primary Completion: 2029-05-31
• Study Completion: 2029-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 208

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Blood Biomarkers	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	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.
Diffusion Tensor Imaging	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	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 .
Sympathetic Reactivity	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	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.
Near Point Convergence	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	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.
King-Devick test	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	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.

Secondary Outcome Measures

Name	Time	Method
Neurite Orientation Dispersion and Density Imaging (NODDI)	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	NODDI metrics will be derived from the the diffusion tensor images using the NODDI toolbox v1.0 in Matlab. Maps of neurite density (ND), orientation dispersion (OD), and intracellular volume fraction (ICVF) will be generated.
Resting-state functional connectivity	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Resting-state connectivity will be examined throughout the whole brain and specific seeded regions including the dorsolateral prefrontal cortex (DLPFC), angular gyrus, and cingulate gyrus.
Cardiovagal baroreflex sensitivity	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Spontaneous cardiovagal baroreflex sensitivity (cBRS) will be collected over the last 5 minutes before the CPT. Baroreflex sequences of 4 consecutive cardiac cycles will be captured using WinCPRS software, for which directional changes in the R-R interval and corresponding systolic blood pressure will be identified. Sequences will be detected when changes in systolic blood pressure are ≥1mmHg and the variation in R-R interval is ≥5miliseconds. Only sequences with an R2 ≥0.85 will be deemed acceptable. The mean of the regression slope will be calculated as the cBRS gain and used for analysis
Heart rate variability	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Leading up to and during the cold pressor test (CPT) heart rate will be monitored via 3-lead ECG. Resting-state heart rate variability and spontaneous cardiovagal baroreflex sensitivity (cBRS) will be monitored over the last 5 minutes before the CPT. Using the R-R interval data collected from the ECG recordings during 5 minutes of paced breathing, time domain analyses will be performed to estimate overall heart rate variability and provide insight into cardiac parasympathetic activity.
Cognition	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Cognitive function will be measured using the NIH Toolbox Cognition Battery, which has excellent reliability and validity to measure cognition in young adults, and has construct validity among those with TBI. Multiple forms will minimize learning effects. This battery examines 5 cognitive domains (executive function, episodic memory, language, working memory, and processing speed) and takes 20 minutes to complete on a tablet.
Cerebral Blood Flow	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Perfusion imaging will be acquired to examine cerebral blood flow.
Metabolomics	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Mitochondrial respiration related metabolites, including pyruvate, acetyl-CoA, citrate, isocitrate, alpha-ketogluterate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate will be assessed on blood samples. The aggregation of all metabolomic data will provide a comprehensive overview of the homeostasis of the participant following repetitive head injury.
Quantitative Susceptibility Mapping	Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session	Quantitative Susceptibility Mapping of whole brain, as well as regions of interest analysis, will be conducted to inspect the tissue and brain architectural response to head impacts and omega-3 fatty acid supplementation.

Trial Locations

Locations (1)

Indiana University School of Public Health; 🇺🇸 Bloomington, Indiana, United States