Derivatives of Omega-3 HUFA as Biomarkers of Traumatic Brain Injury

Study Overview
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Brief Summary
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This is a Phase 2 clinical trial designed to obtain data on relationships between potentially therapeutic doses of n-3 HUFA (highly unsaturated fatty acids) and their bioactive molecular derivatives, synaptamide, 17-hydroxy-DHA, and D-series resolvins, on clinical outcomes after TBI.

Official Title
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Traumatic Brain Injury Recovery With n-3 Highly Unsaturated Fatty Acids (HUFAs): A Biomarker-driven Approach

Conditions
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TBI

Intervention / Treatment
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* Drug: Omega 3 fatty acid
* Dietary Supplement: Safflower seed oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 Documented/ verified TBI Ability to swallow study agent within 48h of injury If a sexually active female who is able to get pregnant, must be already taking birth control (prescription contraception) Visual acuity/ hearing adequate for testing Fluency in English or Spanish Ability to provide informed consent for themselves Co-enrolled in PARC-TBI protocol (IRB protocol #825783) or TRACK-TBI (IRB protocol #825503) GCS 13-15 Exclusion Criteria: Unstable respiratory or hemodynamic status Evidence of penetrating brain injury Requirement for craniotomy or craniectomy Evidence of serious infectious complications Acute ischemic heart disease or abnormal heart rhythm History of abnormality in liver function History or evidence of active malignancy History of diabetes History of pre-existing neurologic disorder, such as dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation neuropsychological results History of pre-existing disabling Axis I psychiatric disorder, such as major depression, schizophrenia, bipolar disorder or dementia Allergy to omega-3 fatty acid ethyl esters or any ingredient of the study agent. Known allergy to Safflower seed oil or ragweed plants Consumption of fish or seafood 3 or more times per week on average or regular administration of omega-3 supplements (e.g., cod liver oil, borage oil, fish oil or evening primrose oil) defined as an average of 250 mg/day of n-3 HUFAs, over the previous 3 months. Pregnancy or breast-feeding Prisoners or patients in custody Allergy, hypersensitivity, or intolerance to fish oils or omega-3 fats which are found in fish. Use of anticoagulant medications or aspirin more than once per week within the last three months Enrollment in any concurrent research protocols that would interfere with participant safety or research data integrity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1,000mg/day n-3 HUFA<br>Subjects will take one capsule daily starting at study enrollment (within 24 hours of injury) for 14 consecutive days. | Drug: Omega 3 fatty acid<br>* LOVAZA is an FDA approved drug that is lawfully marketed in the United States by GlaxoSmithKline. There is no intent to use the results of this study to support a change in the labeling or the advertising of the drug. The highest dose administered for the study is the recommended prescribed dose of LOVAZA, therefore not creating greater risk. The patient population and route of administration will not significantly increase the risk associated with the use of the product. We will be using this drug under an IND exemption.<br>* Other names: LOVAZA;|
| Experimental: 4,000 mg/day n-3 HUFA<br>Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days. | Drug: Omega 3 fatty acid<br>* LOVAZA is an FDA approved drug that is lawfully marketed in the United States by GlaxoSmithKline. There is no intent to use the results of this study to support a change in the labeling or the advertising of the drug. The highest dose administered for the study is the recommended prescribed dose of LOVAZA, therefore not creating greater risk. The patient population and route of administration will not significantly increase the risk associated with the use of the product. We will be using this drug under an IND exemption.<br>* Other names: LOVAZA;|
| Placebo Comparator: 1 capsule safflower seed oil<br>Subjects will take 1 capsule daily starting at enrollment (within 24 hours of injury) for 14 consecutive days. | Dietary Supplement: Safflower seed oil<br>* Safflower seed oil is a commonly used dietary supplement. It has been chosen to be used as a comparative to the LOVAZA because of its non-omega-3 fats. There will be no increased risk due to dosage, route of administration, or patient population.<br>|
| Placebo Comparator: 4 capsules safflower seed oil<br>Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days. | Dietary Supplement: Safflower seed oil<br>* Safflower seed oil is a commonly used dietary supplement. It has been chosen to be used as a comparative to the LOVAZA because of its non-omega-3 fats. There will be no increased risk due to dosage, route of administration, or patient population.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship of varying doses of n-3 HUFAs on blood levels of the following bioactive metabolites | Bioactive metabolites being looked at are: synaptamide (n-docosahexaenoylethanolamine), 17-hydroxy-DHA, and D-series resolvins and determine relationship of n-3 HUFAs on blood levels of indicators of neuroinflammatory damage including Brain Derived Neurotrophic Factor (BDNF) in humans over 14 days after TBI. | 14 days consecutively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship of n-3 HUFA blood levels and clinical outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) | Clinical outcomes will include functional outcomes and will be assessed by using the TBI Common Data Elements Outcome battery. The analysis will focus on the Glasgow Outcome Scale-Extended (GOS-E) an ordinal scale based on a structured questionnaire which is universally used in TBI clinical studies. | 14 days consecutively | 
| Evalute potential adverse events | Evaluate potential adverse side effects including gastrointestinal tolerance and adverse neurological outcomes. | 14 days consecutively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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synaptamide, TBI, DHA, omega-3 highly unsaturated fatty acids