Omega-3 Fatty Acids and Subconcussive Head Impacts
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-30
SponsorIndiana University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Between age 18-30
Current or former soccer player
At least 5 years of soccer heading experience
Have internet access
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Omega-3 Fatty Acids (EPA plus DHA)
Dietary supplementDHA+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 \[a total of 3.4 g/d: DHA (2.4 g), EPA (1.0 g)\].
Organic soybean oil
Dietary supplementWe 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
Other interventionA 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.
Treatment groups
208 Participants
are divided into 2 treatment groupsGroup A: Placebo: Organic soybean oil pillsPlacebo comparator 2 interventions
Group B: Omega-3 Fatty Acids (EPA plus DHA)Active comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session2
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 .
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session3
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session4
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading sessionSecondary outcomes
1
Neurite Orientation Dispersion and Density Imaging (NODDI)
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session2
Resting-state functional connectivity
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session3
Cardiovagal baroreflex sensitivity
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
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session4
Heart rate variability
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.
Time frame
Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading sessionOther outcomes
1
Genetic markers
Several genetic markers that are known to associate with brain vulnerability will be assessed and regressed against our outcome measures. These genetic markers include, but not limited to, DARC, APOE, KIAA0319, BDNF, TPH2, COMT. Each marker will be compared to the other outcome measures to understand the full effect of the intervention on the genetic markers as a whole.
Time frame
Baseline2
ADHD
Participants who meet criteria for ADHD diagnosis will be analyzed to address the interactive effects of DHA+EPA and head impacts in ADHD.
Time frame
BaselineSponsors and contacts
Click on the lead sponsor to view all of their trials.
Indiana University
Lead sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
Source ClinicalTrials.gov