NCT03345550

OPTIMA-TBI Pilot Study

Pilot Study of Omega-3 Polyunsaturated Fatty Acid Treatment in Mild Acute TBI (OPTIMA-TBI Pilot)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: University of Michigan · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is a double-blind, randomized controlled trial comparing the effect of omega-3 fatty acid versus placebo on blood biomarkers of brain injury, inflammation and neurogenesis.

Detailed description

Primary brain injury, the initial physical injury to brain tissue post-trauma, responds only to measures that prevent TBI from occurring in the first place. However, secondary brain injury, a complex cascade of events causing additional brain injury following primary brain injury, is more amenable to pharmacologic treatment. Neuroinflammation is one of the recognized mechanisms of secondary brain injury. In response to primary brain injury, activated microglia and injured neurons both release signaling proteins including cytokines and chemokines. Ω-3 and ω-6 fatty acids are major components of immune cells and neuronal cell membranes. They are also precursors to neuromodulatory lipids such as eicodanoids, endovanilloids and endocannabinoids that have antinociceptive and anxiolytic properties. Docosahexaenoic acid (DHA) is one of the most abundant fatty acid components of brain cell membrane phospholipids. In rodent model studies, dietary supplementation with omega-3 fatty acids (eicosapentaenoic acid \[EPA\] and docosahexaenoic acid \[DHA\]) decreased secondary axonal injury, attenuated endoplasmic reticulum stress response, decreased neuroinflammation post-TBI, and improved short and long-term neurologic outcomes. Additionally, DHA supplementation post-TBI enhances neurogenesis by counteracting reductions in neuroplasticity biomarkers such as brain-derived neurotrophic factor. Furthermore, DHA deficient rodents are more likely to have a greater amount of axonal injury and slower recovery neurologic recovery post-TBI. To our knowledge there are no human studies examining the effect of omega-3 fatty acid supplementation post-TBI on functional, symptomatic and neurologic outcomes. However, a study of collegiate football players who were randomized to 2, 4 or 6g/day of DHA or placebo for a total of 189 days (including 80 pre-season days). Irrespective of the dose of DHA supplementation, those receiving DHA had lower values of serum neurofilament light chain, a biomarker of axonal injury, than those receiving placebo.

Conditions

• Mild Traumatic Brain Injury

Interventions

Type	Name	Description
DRUG	Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules.	Participants will be randomized to receive fish oil 1000 mg (contains 500 mg DHA \& 100 mg EPA) or placebo capsules.
DRUG	Placebo - Cap	Participants will be randomized to receive fish oil 1000 mg (contains 500 mg DHA \& 100 mg EPA) or placebo capsules (olive oil capsules that look identical to the intervention DHA+EPA).

Timeline

• Start date: 2017-09-12
• Primary completion: 2021-07-27
• Completion: 2021-07-27
• First posted: 2017-11-17
• Last updated: 2023-05-23
• Results posted: 2023-05-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study