Omega-3 Fatty Acids, Subconcussive Head Impact
Conditions
Keywords
Subconcussive brain injury, TBI, Soccer heading, Omega-3 fatty acids
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.
Interventions
DIETARY_SUPPLEMENTOmega-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 \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].
DIETARY_SUPPLEMENTOrganic 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.
OTHERSoccer 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.
Sponsors
Indiana University
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Several co-investigators and undergraduate researchers will remain masked throughout the trial.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTKei Kawata
Outcome results
None listed