The Effects of Fish Oil Supplementation on the Brain Health of Collegiate Football Athletes

Sponsor

University of Arizona (Other)

Overall Status

Completed

CT.gov ID

NCT04796207

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Determine if the daily docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) supplement will reduce serum levels of biomarkers of sub-concussion injuries over a course of American football season among collegiate football athletes.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury (TBI) Chronic Traumatic Encephalopathy (CTE)	Dietary Supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules Dietary Supplement: High Oleic Safflower Oil Capsules	N/A

Detailed Description

American football is one of the most popular sports in the U.S. Yet this sport is associated with increased risk of concussion (also known as mild traumatic brain injury, or mTBI) and sub-concussive injury from repeated head impacts (RHI) due to the aggressive and high-speed nature of the game. Current protective equipment used by players are not sufficient to reduce concussion incidence and severity, nor are there any therapeutics available to prevent concussion. This study is a randomized, double-blind, placebo controlled trial to determine if an omega-3 polyunsaturated fatty acid (PUFA) fish oil supplement containing 3.0 grams of docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) can reduce blood biomarkers of sub-concussion injuries compared to placebo (high-oleic safflower oil) over a course of the American football season among collegiate football athletes.

The dosage of DHA/EPA used in this study is generally safe, and procedures involved, monthly blood draws, surveys, and Magnetic Resonance Imaging (MRI), pose minimal risks to participants. While this study provides no direct benefit to participants, successful outcomes of this study can benefit the society by shedding light on development of potential preventative therapeutics for sports-induced mTBI and brain injury from RHI. The risk-benefit profile is appropriate for conducting this study. Based on preclinical studies and previous clinical study results, the investigators expect that in comparison to placebo treatment, DHA and EPA treatment throughout the course of one American football season can maintain lower levels of sub-concussion associated biomarkers, inflammatory cytokines, and cardiovascular risk markers. The investigators also expect participants treated with DHA and EPA to have lower brain MRI imaging markers of sub concussion injury.

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized to treatment (3 grams DHA and EPA (2:1 weight ratio)) or placebo (3 grams high-oleic safflower oil) in a 1:1 allocation ratio based on their position on the football team and roster depth (starter vs. non-starter). Participants will be recruited as a single cohort. After screening, participants will be treated with DHA and EPA or matching placebo for 25 weeks (a full course of an American football season, including summer camp training sessions). A follow-up visit is scheduled 7 weeks after the final dosing at week 32 for recovery and adverse event evaluation.Participants will be randomized to treatment (3 grams DHA and EPA (2:1 weight ratio)) or placebo (3 grams high-oleic safflower oil) in a 1:1 allocation ratio based on their position on the football team and roster depth (starter vs. non-starter). Participants will be recruited as a single cohort. After screening, participants will be treated with DHA and EPA or matching placebo for 25 weeks (a full course of an American football season, including summer camp training sessions). A follow-up visit is scheduled 7 weeks after the final dosing at week 32 for recovery and adverse event evaluation.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Study personnel will be kept blind to treatment assignments. The treatment assignment for each participant will be available to the investigator in a sealed envelope that may be opened only in the case of a serious adverse event which the investigator feels cannot be adequately treated without knowing the identity of the study medication. Code breakers will be collected and reviewed at the end of the study. If the blinding has been broken, then the investigator will provide documentation regarding the fact and indicate the other staff that received this information.

Primary Purpose:

Prevention

Official Title:

Study of Effect of Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) Supplementation on Biomarkers of Sub-Concussion Injuries in American Football

Actual Study Start Date :

May 28, 2019

Actual Primary Completion Date :

Jan 28, 2020

Actual Study Completion Date :

Jan 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fish Oil Capsules Participants in the treatment arm will receive 3 grams of DHA and EPA (2:1 weight ratio) 3 times a week for 25-weeks during regular football season.	Dietary Supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules The Treatment Arm intervention consists of providing participants with 3 grams of DHA and EPA (2:1 weight ratio) in capsular form. In order to meet the required 3 grams of DHA and EPA, participants were given 6 capsules to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.
Placebo Comparator: Safflower Oil Capsules Participants in the treatment arm will receive 3 grams of high-oleic safflower oil) in a 1:1 allocation ratio for 25-weeks during regular football season.	Dietary Supplement: High Oleic Safflower Oil Capsules The Placebo Arm intervention consists of providing participants with 3 grams of high-oleic safflower oil in a 1:1 allocation ratio in capsular form. In order to maintain the "study masking", participants in the Placebo Arm were given 6 capsules (the same as the Treatment Arm) to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.

Arm

Intervention/Treatment

Experimental: Fish Oil Capsules

Participants in the treatment arm will receive 3 grams of DHA and EPA (2:1 weight ratio) 3 times a week for 25-weeks during regular football season.

Dietary Supplement: Fish Oil (DPA+EPA 2:1 ratio) Capsules

The Treatment Arm intervention consists of providing participants with 3 grams of DHA and EPA (2:1 weight ratio) in capsular form. In order to meet the required 3 grams of DHA and EPA, participants were given 6 capsules to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.

Placebo Comparator: Safflower Oil Capsules

Participants in the treatment arm will receive 3 grams of high-oleic safflower oil) in a 1:1 allocation ratio for 25-weeks during regular football season.

Dietary Supplement: High Oleic Safflower Oil Capsules

The Placebo Arm intervention consists of providing participants with 3 grams of high-oleic safflower oil in a 1:1 allocation ratio in capsular form. In order to maintain the "study masking", participants in the Placebo Arm were given 6 capsules (the same as the Treatment Arm) to be taken with meals (preferably breakfast, although capsules were provided at lunch when they couldn't be provided at breakfast). Capsules were given 3 times a week during the regular football season.

Outcome Measures

Primary Outcome Measures

Changes in brain biomarkers due to sub-concussion injury - Nf-L [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma brain biomarker Neurofilament Light Chains (Nf-L) due to sub-concussion injury from baseline to predetermined measurement time points. Nf-L (neuron specific intermediate proteins) are released upon injury to neurons and axons. Measured in picograms per milliliter (pg/ml)
Changes in brain biomarkers due to sub-concussion injury - Tau [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma brain biomarker Tau protein due to sub-concussion injury from baseline to predetermined measurement time points. Tau protein accumulates in the brain after injury. Tau protein is measured in picograms per milliliter (pg/ml)
Changes in brain biomarkers due to sub-concussion injury - UCH-L1 [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma brain biomarker Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) due to sub-concussion injury from baseline to predetermined measurement time points. UCH-L1 levels are elevated in the cerebrospinal fluid (CSF) and serum for several days after severe traumatic brain injury. UCH-L1 is measured in nanograms per milliliter (ng/ml)
Changes in sub-concussion injury related inflammation biomarkers - CRP [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma inflammation biomarker C-reactive Protein (CRP), a marker of general inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. CRP is measured in milligrams per liter (mg/L)/
Changes in sub-concussion injury related inflammation biomarkers - TNF-α [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma inflammation biomarker Tumor Necrosis Factor-alpha (TNF-α), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. TNF-α is measured in picograms per milliliter (pg/ml).
Changes in sub-concussion injury related inflammation biomarkers - IL-6 [Baseline; then once a month until the end of the study, up to 8 months.]
This primary outcome covers the change in the plasma inflammation biomarker Interleukin-6 (IL-6), a cytokine and mediator of inflammation, due to sub-concussion injury from baseline to predetermined measurement time points. IL-6 is measured in picograms per milliliter (pg/ml)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 25 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

University of Arizona National Collegiate Athletic Association (NCAA) Division I American football athletes cleared to participate in university athletics as determined by the team physician.

Exclusion Criteria:

Chronic daily anti-inflammatory drugs (>20 d).
Medications for blood lipids.
Active fish oil or omega-3 fatty acid supplementation.
Consumption of more than two servings of fish per week.
Injured and unable to participate in regularly schedule conditioning or competitions.
Acute concussion experienced within 30 days of starting the study.
Fish allergies.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85721

Sponsors and Collaborators

University of Arizona

Investigators

Principal Investigator: Floyd Chilton, Ph.D., University of Arizona
Principal Investigator: Roberta Brinton, Ph.D., University of Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Floyd Chilton, Professor, Department of Nutritional Sciences Director, Precision Nutrition & Wellness Initiative Associate Director,The BIO5 Institute, University of Arizona

ClinicalTrials.gov Identifier:

NCT04796207

Other Study ID Numbers:

IRB1904553365

First Posted:

Mar 12, 2021

Last Update Posted:

Mar 12, 2021

Last Verified:

Mar 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Floyd Chilton, Professor, Department of Nutritional Sciences Director, Precision Nutrition & Wellness Initiative Associate Director,The BIO5 Institute, University of Arizona

CTE (Chronic Traumatic Encephalopathy)

mTBI (Mild Traumatic Brain Injury)

Concussion

MRI

Nf-L (Neurofilament Light Chain)

Biomarker

Football

Additional relevant MeSH terms:

Brain Injuries

Brain Injuries, Traumatic

Brain Diseases

Chronic Traumatic Encephalopathy

Study Results

No Results Posted as of Mar 12, 2021