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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: TBI
• Intervention / Treatment: Drug: Omega 3 fatty acid; Dietary supplement: Safflower seed oil

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-55
2. Documented/ verified TBI
3. Ability to swallow study agent within 48h of injury
4. If a sexually active female who is able to get pregnant, must be already taking birth control (prescription contraception)
5. Visual acuity/ hearing adequate for testing
6. Fluency in English or Spanish
7. Ability to provide informed consent for themselves
8. Co-enrolled in PARC-TBI protocol (IRB protocol #825783) or TRACK-TBI (IRB protocol #825503)
9. GCS 13-15

Exclusion Criteria:

1. Unstable respiratory or hemodynamic status
2. Evidence of penetrating brain injury
3. Requirement for craniotomy or craniectomy
4. Evidence of serious infectious complications
5. Acute ischemic heart disease or abnormal heart rhythm
6. History of abnormality in liver function
7. History or evidence of active malignancy
8. History of diabetes
9. 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
10. History of pre-existing disabling Axis I psychiatric disorder, such as major depression, schizophrenia, bipolar disorder or dementia
11. Allergy to omega-3 fatty acid ethyl esters or any ingredient of the study agent.
12. Known allergy to Safflower seed oil or ragweed plants
13. 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.
14. Pregnancy or breast-feeding
15. Prisoners or patients in custody
16. Allergy, hypersensitivity, or intolerance to fish oils or omega-3 fats which are found in fish.
17. Use of anticoagulant medications or aspirin more than once per week within the last three months
18. Enrollment in any concurrent research protocols that would interfere with participant safety or research data integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Ramon Diaz-Arrastia, MD, PhD, University of Pennsylvania Perelman School of Medicine

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 7, 2016
• First Posted (Estimate): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: DHA; TBI; omega-3 highly unsaturated fatty acids; synaptamide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 826109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No