Mechanistic Investigation of Omega-3 Fatty Acids Pretreatment Effects on Subconcussive Brain Injury
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Blood Biomarkers
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
Several co-investigators and undergraduate researchers will remain masked throughout the trial.
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Organic soybean oil (Dietary Supplement)
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.
干预措施: Soccer Heading Model (Other)
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)].
干预措施: Omega-3 Fatty Acids (EPA plus DHA) (Dietary Supplement)
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)].
干预措施: Soccer Heading Model (Other)
结局指标
主要结局
Blood Biomarkers
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)
- Cerebral Blood Flow(Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session)
- Metabolomics(Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session)
- Quantitative Susceptibility Mapping(Baseline, 24 hours following 1st and 2nd heading sessions, 7 days following the 2nd heading session)
研究者
Keisuke Kawata
Associate Professor
Indiana University