Not provided
Not provided
Not provided
Not provided
Slow accrual of patients, lack of financial resources
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Omega-3 Polyunsaturated Fatty Acid Treatment Arm | Experimental | Participants randomized to this study arm will receive 6g DHA+EPA for one month followed by 1.2 g DHA+EPA for two months. Capsules contain fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. |
|
| Placebo Arm | Placebo Comparator | Participants randomized to this study arm will receive placebo drug for 3 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules. | Drug | Participants will be randomized to receive fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker Endpoints (NFL) | Neuronal injury measured by Neurofilament Light Chain (NFL). Samples will be analyzed using a digital immunoassay based on a single molecule counting technology. | Baseline,3 months |
| Biomarker Endpoint (Inflammation) | We will measure serum levels of high sensitivity C-Reactive Protein (CRP) | 3 months |
| Biomarker Endpoint (Neurogenesis) | Serum levels of brain derived neurotrophic factor (BDNF) | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Delayed Functional Recovery | Delayed functional recovery will be defined as a Glasgow Outcome Scale Extended (GOSE) <8 at 3 months. Scores range from 1-8. 8 is Upper good recovery and 1 is death | 3 months |
| Gastrointestinal Distress |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Impairment | Cognitive impairment will be defined by a battery of neurocognitive tests including the Montreal Cognitive Assessment (MOCA), Hopkins Verbal Learning Test (HVLT), Trails A and B, Brief Visuospatial Memory Test (BVMT), Stroop Test, Wechsler Test of Adult Reading (WTAR), Brief Test of Attention, (BTA), Wisconsin Card Sorting Test (WCST) and COWAT (Controlled Oral Word Association Test). The WTAR will be used as an estimate of IQ and the neurocognitive test T-scores of interest will be compared against the subject's IQ T-score. The standard deviation (SD) of each T-score is 10. Each of the subject's neurocognitive tests is considered aberrant if it is more than 2 SD below the subject's IQ T-score. A subject is considered cognitively impaired if at least 2 (based on the .05 rule; 5 out of every 100 test scores will be outside of expected range by chance alone) out of the T-scores are aberrant. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Frederick Korley, M.D., Ph.D. | Department of Emergency Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Omega-3 Polyunsaturated Fatty Acid Treatment Arm | Participants randomized to this study arm received 6g DHA+EPA for one month followed by 1.2 g DHA+EPA for two months. Capsules contain fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules.: Participants were randomized to receive fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. |
| FG001 | Placebo Arm | Participants randomized to this study arm received placebo drug for 3 months. Placebo - Cap: Participants were 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Omega-3 Polyunsaturated Fatty Acid Treatment Arm | Participants randomized to this study arm received 6g DHA+EPA for one month followed by 1.2 g DHA+EPA for two months. Capsules contain fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules.: Participants were randomized to receive fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Biomarker Endpoints (NFL) | Neuronal injury measured by Neurofilament Light Chain (NFL). Samples will be analyzed using a digital immunoassay based on a single molecule counting technology. | For some of the assays, some individuals' data was not available. | Posted | Median | Inter-Quartile Range | picograms per ml | Baseline,3 months |
|
3 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Omega-3 Polyunsaturated Fatty Acid Treatment Arm | Participants randomized to this study arm received 6g DHA+EPA for one month followed by 1.2 g DHA+EPA for two months. Capsules contain fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules.: Participants were randomized to receive fish oil 1000 mg (contains 500 mg DHA & 100 mg EPA) or placebo capsules. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Frederick Korley | University of Michigan | 734 647-0261 | korley@med.umich.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 8, 2018 | Jul 26, 2022 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001924 | Brain Concussion |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004281 | Docosahexaenoic Acids |
| D005395 | Fish Oils |
| ID | Term |
|---|---|
| D015525 | Fatty Acids, Omega-3 |
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo - Cap | Drug | 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). |
|
GI distress is measured by number of individuals who experienced it.
| 3 months |
| Clinically Significant Bleeding | Clinically significant bleeding distress is measured by number of individuals who experienced it. | 3 months |
| 3 months |
| Moderate/Severe Post-Concussive Symptoms | Moderate/severe post-concussive symptoms will be defined as the presence of any one or more of the following: headaches, dizziness, general malaise, excessive fatigue, or noise intolerance, irritability, emotional lability, depression, or anxiety, subjective complaints of concentration or memory difficulty, insomnia, reduced tolerance to alcohol, preoccupation with these symptoms and fear of permanent brain damage. These will be self-reported by the patient. | 3 months |
| BG001 | Placebo Arm | Participants randomized to this study arm received placebo drug for 3 months. Placebo - Cap: Participants were 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). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo Arm | Participants randomized to this study arm received placebo drug for 3 months. Placebo - Cap: Participants were 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). |
|
|
|
| Primary | Biomarker Endpoint (Inflammation) | We will measure serum levels of high sensitivity C-Reactive Protein (CRP) | While serum was collected no CRP data or measurements were made or can be made now or in the future. | Posted | 3 months |
|
|
| Primary | Biomarker Endpoint (Neurogenesis) | Serum levels of brain derived neurotrophic factor (BDNF) | While serum was collected, no BDNF data or measurements were collected or can be made now or in the future. | Posted | 3 months |
|
|
| Secondary | Delayed Functional Recovery | Delayed functional recovery will be defined as a Glasgow Outcome Scale Extended (GOSE) <8 at 3 months. Scores range from 1-8. 8 is Upper good recovery and 1 is death | Posted | Count of Participants | Participants | 3 months |
|
|
|
|
| Secondary | Gastrointestinal Distress | GI distress is measured by number of individuals who experienced it. | Posted | Count of Participants | Participants | 3 months |
|
|
|
| Secondary | Clinically Significant Bleeding | Clinically significant bleeding distress is measured by number of individuals who experienced it. | All 22 participants were analyzed on an Intention to Treat analysis. | Posted | Count of Participants | Participants | 3 months |
|
|
|
| Other Pre-specified | Cognitive Impairment | Cognitive impairment will be defined by a battery of neurocognitive tests including the Montreal Cognitive Assessment (MOCA), Hopkins Verbal Learning Test (HVLT), Trails A and B, Brief Visuospatial Memory Test (BVMT), Stroop Test, Wechsler Test of Adult Reading (WTAR), Brief Test of Attention, (BTA), Wisconsin Card Sorting Test (WCST) and COWAT (Controlled Oral Word Association Test). The WTAR will be used as an estimate of IQ and the neurocognitive test T-scores of interest will be compared against the subject's IQ T-score. The standard deviation (SD) of each T-score is 10. Each of the subject's neurocognitive tests is considered aberrant if it is more than 2 SD below the subject's IQ T-score. A subject is considered cognitively impaired if at least 2 (based on the .05 rule; 5 out of every 100 test scores will be outside of expected range by chance alone) out of the T-scores are aberrant. | Not Posted | 3 months | Participants |
| Other Pre-specified | Moderate/Severe Post-Concussive Symptoms | Moderate/severe post-concussive symptoms will be defined as the presence of any one or more of the following: headaches, dizziness, general malaise, excessive fatigue, or noise intolerance, irritability, emotional lability, depression, or anxiety, subjective complaints of concentration or memory difficulty, insomnia, reduced tolerance to alcohol, preoccupation with these symptoms and fear of permanent brain damage. These will be self-reported by the patient. | Not Posted | 3 months | Participants |
| Post-Hoc | Glial Fibrillary Acidic Protein (GFAP) | Missing blood samples due to loss of follow-up. | Posted | Mean | Inter-Quartile Range | picograms per ml | 3 months |
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 3 |
| 22 |
| EG001 | Placebo Arm | Participants randomized to this study arm received placebo drug for 3 months. Placebo - Cap: Participants were 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). | 0 | 22 | 0 | 22 | 0 | 22 |
Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D016489 | Head Injuries, Closed |
| D014947 | Wounds and Injuries |
| D014949 | Wounds, Nonpenetrating |
| D008055 |
| Lipids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D009821 | Oils |
| 1 month |
|
|
| 3 month |
|
|