Mild Traumatic Brain InjuryPhase 2OPTIMANCT03345550
OPTIMA-TBI Pilot Study
A Phase 2 study of Mild Traumatic Brain Injury, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mild Traumatic Brain Injury
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2017to 27 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals presenting to the emergency department (ED) within 24 hours of injury, who meet the American Congress of Rehabilitation Medicine (ACRM)'s definition of having mild traumatic brain injury (mTBI) will be eligible
- The ACRM defines mTBI as a traumatically-induced physiological disruption of brain function as a consequence of the head being struck, striking an object, or undergoing an acceleration/deceleration movement without direct external head trauma and resulting in at least one of the following:
- any period of loss of consciousness (LOC)
- any loss of memory for events immediately before or after the injury
- any alteration in mental state at the time of the injury (eg, feeling dazed, disoriented, or confused)
- focal neurological deficit(s) that may or may not be transient
Who cannot join
- GCS<13 at any time during ED stay.
- Significant polytrauma including: bony fracture or solid organ injury
- Study medication cannot be administered within 24 hours of injury
- Patient cannot be relied on to complete follow-up (i.e. no reliable telephone number, substance dependence, homeless)
- Cannot communicate in English
- Take an anticoagulant (coumadin or a novel oral anticoagulant) daily
Show all 11Show fewer
- Age less than 18 years or greater than 65 years
- Patients already taking fish oil supplements daily
- History of cognitive impairment
- Allergic to fish/fish oil
- Pregnant women (self-reported)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of Omega-3 Polyunsaturated Fatty Acid Treatment in Mild Acute TBI (OPTIMA-TBI Pilot)
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.
Read the 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
- Being tested
- Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules., Placebo - Cap
- Medical subject headings
- Brain Concussion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Placebo - CapDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Omega-3 Polyunsaturated Fatty Acids (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. Receives: Drug: Placebo - Cap |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline,3 months
Biomarker Endpoint (Inflammation)
We will measure serum levels of high sensitivity C-Reactive Protein (CRP)
Measured: 3 months
Biomarker Endpoint (Neurogenesis)
Serum levels of brain derived neurotrophic factor (BDNF)
Measured: 3 months
Secondary outcomes (3)
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
Measured: 3 months
Gastrointestinal Distress
GI distress is measured by number of individuals who experienced it.
Measured: 3 months
Clinically Significant Bleeding
Clinically significant bleeding distress is measured by number of individuals who experienced it.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start12 Sep 2017
- Primary completion27 Jul 2021
- Study completion27 Jul 2021
Why it stopped: Slow accrual of patients, lack of financial resources
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mild Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frederick Korley, MD, PhD, University of Michigan
- Investigators
- Frederick Korley, M.D., Ph.D., Principal investigator, Department of Emergency Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03345550
- Sponsor's protocol ID
- HUM00129045
- Acronym
- OPTIMA
- Status last verified
- Apr 2023
- First submitted
- 12 Nov 2017
- Last updated
- 23 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Omega-3 Polyunsaturated Fatty Acid Treatment in Mild Acute TBI (OPTIMA-TBI Pilot)
- ClinicalTrials.gov ID
- NCT03345550
- Acronym / sponsor ID
- OPTIMA / HUM00129045
- Conditions
- Mild Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual of patients, lack of financial resources
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- 12 Sep 2017 (actual)
- Primary completion
- 27 Jul 2021 (actual)
- Study completion
- 27 Jul 2021 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 23 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omega-3 Polyunsaturated Fatty Acid Treatment Arm | Experimental | Drug: Omega-3 Polyunsaturated Fatty Acids (Fish Oil 1000 mg (contains 500 mg DHA & 100 mg EPA)) or placebo capsules.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 | Drug: Placebo - CapParticipants randomized to this study arm will receive placebo drug for 3 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Individuals presenting to the emergency department (ED) within 24 hours of injury, who meet the American Congress of Rehabilitation Medicine (ACRM)'s definition of having mild traumatic brain injury (mTBI) will be eligible
- The ACRM defines mTBI as a traumatically-induced physiological disruption of brain function as a consequence of the head being struck, striking an object, or undergoing an acceleration/deceleration movement without direct external head trauma and resulting in at least one of the following:
- any period of loss of consciousness (LOC)
- any loss of memory for events immediately before or after the injury
- any alteration in mental state at the time of the injury (eg, feeling dazed, disoriented, or confused)
Key exclusion criteria (11 listed)
- GCS<13 at any time during ED stay.
- Significant polytrauma including: bony fracture or solid organ injury
- Study medication cannot be administered within 24 hours of injury
- Patient cannot be relied on to complete follow-up (i.e. no reliable telephone number, substance dependence, homeless)
- Cannot communicate in English
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Omega-3 Polyunsaturated Fatty Acid Treatment Arm |
| Placebo - CapParticipants 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). | Drug | Placebo Arm |
Primary outcome
Biomarker Endpoints (NFL)
Time frame: Baseline,3 months
Neuronal injury measured by Neurofilament Light Chain (NFL). Samples will be analyzed using a digital immunoassay based on a single molecule counting technology.
Biomarker Endpoint (Inflammation)
Time frame: 3 months
We will measure serum levels of high sensitivity C-Reactive Protein (CRP)
Biomarker Endpoint (Neurogenesis)
Time frame: 3 months
Serum levels of brain derived neurotrophic factor (BDNF)
3 secondary outcomes
Delayed Functional Recovery
Time frame: 3 months
Gastrointestinal Distress
Time frame: 3 months
Clinically Significant Bleeding
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederick Korley, M.D., Ph.D. principal investigator
Department of Emergency Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Mild Traumatic Brain Injury, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker Endpoints (NFL) (time frame: Baseline,3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.