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

Sponsor

University of Pennsylvania (Other)

Overall Status

Recruiting

CT.gov ID

NCT02990091

Collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
TBI	Drug: Omega 3 fatty acid Dietary Supplement: Safflower seed oil	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Diagnostic

Official Title:

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

Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1,000mg/day n-3 HUFA Subjects will take one capsule daily starting at study enrollment (within 24 hours of injury) for 14 consecutive days.	Drug: Omega 3 fatty acid 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. Other Names: LOVAZA
Experimental: 4,000 mg/day n-3 HUFA Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.	Drug: Omega 3 fatty acid 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. Other Names: LOVAZA
Placebo Comparator: 1 capsule safflower seed oil Subjects will take 1 capsule daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.	Dietary Supplement: Safflower seed oil 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.
Placebo Comparator: 4 capsules safflower seed oil Subjects will take 2 capsules twice daily starting at enrollment (within 24 hours of injury) for 14 consecutive days.	Dietary Supplement: Safflower seed oil 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.

Outcome Measures

Primary Outcome Measures

Relationship of varying doses of n-3 HUFAs on blood levels of the following bioactive metabolites [14 days consecutively]
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.

Secondary Outcome Measures

Relationship of n-3 HUFA blood levels and clinical outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) [14 days consecutively]
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.
Evalute potential adverse events [14 days consecutively]
Evaluate potential adverse side effects including gastrointestinal tolerance and adverse neurological outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.