DHA For The Treatment of Pediatric Concussion Related to Sports Injury

Study ID
042012-055

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Texas Scottish Rite Hospital for Children

Contact


Principal Investigator

Official Title

Docosahexaenoic Acid (DHA) For The Treatment of Pediatric Concussion Related to Sports Injury

Brief Overview


In recent years, media attention has focused on the long-term sequelae of repeated
concussive episodes in professional athletes. The growing understanding of the damage done
by what was once considered a "ding" during a game or match, and the neurologic consequences
of "playing through" or returning to play too soon has led to additional interest in and
concern for pediatric athletes (18 or under) who experience sports-related concussions
during game or practice play.

Because it has only been in recent years that the full scope of damage done by repeated
concussive episodes has come to light, very little research has been done on treatment of
concussion in either adults or children. Brain injuries in children can be especially
problematic, as the brain may continue to develop until the child reaches the age of 24 or
older, so concussion during this time of development may be particularly damaging.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid commonly found in both fish oils and
algae. DHA is known to improve development of the eyes and brain in young children. It is
thought to be an effective anti-inflammatory and anti-oxidant, and since it occurs naturally
and causes very few harmful side effects, it may be a useful compound in the treatment of
pediatric concussion.

This is a feasibility trial of DHA for the treatment of sports concussion in a pediatric
population. The investigators' primary aim is to determine acceptability of randomization
for this compound as well as rate of enrollment given our clinical population. The
investigators' secondary aim is to examine preliminary outcomes. The investigators
hypothesize that subjects who take 2 g of DHA daily for 3 months will see a shorter time to
full recovery and return to play and a shorter time to resolve balance disturbance. These
are good, albeit unvalidated, clinical indicators of concussive recovery.

Summary


This is a double-blind, randomized, placebo-controlled feasibility trial of DHA for the
treatment of pediatric concussion related to sports-injury. The definition used for
concussion is from the Consensus Statement on Concussion in Sport: the 3rd International
Conference on Concussion in Sport (Br J Sports Med 2009;43:Suppl 1 i76-i84
doi:10.1136/bjsm.2009.058248) and will meet the following criteria:

1. Direct blow to the head, face, neck or a blow elsewhere on the body with an "impulsive"
force transmitted to the head.

2. Rapid onset of short-lived impairment of neurologic function in one or more of the
following clinical domains that resolves spontaneously:

1. symptoms: somatic (eg, headache), cognitive (eg, feeling like in a fog) and/or
emotional symptoms (eg, lability).

2. physical signs (eg, loss of consciousness, amnesia).

3. behavioural changes (eg, irritability).

4. cognitive impairment (eg, slowed reaction times).

5. sleep disturbance (eg, drowsiness).

3. No abnormality on standard structural neuroimaging studies, if such neuroimaging
studies are completed for a clinically-indicated reason. Note: neuroimaging is not a
part of this study protocol. Study participants will not undergo neuroimaging as part
of this study.

Subjects will be randomized in a 1:1 fashion. DHA is an omega-3 fatty acid that occurs
naturally in fish oil and algae. There are many dietary supplements containing DHA available
in the marketplace. Martek Biosciences provides an algae-based DHA compound which minimizes
the side effects of "fishiness" in both flavor and "fish burps." The DHA produced by Martek
Biosciences is also used for many infant formula companies in the US. DHA and identical
placebo will be provided by Martek Biosciences.

The DHASCO capsules are supplied as 950 mg capsules with an effective dose of 500 mg DHA per
capsule. The placebo capsules are supplied as 950 mg capsules consisting of 475 mg corn oil
and 475 mg soy oil. Both DHA and placebo are flavored with sweet orange flavoring and
masking agents.

They are supplied in sealed white plastic bottles containing 100-200 capsules per bottle,
depending on dose. Each bottle has the lot number stamped on it. The capsules will be stored
in a dry, locked compartment at room temperature (60 to 75 F). Martek's Quality Assurance
department completes regularly scheduled chemical and long-term stability analyses on each
lot of capsules. If shipments will occur during warmer months, arrangements will be made for
capsules to be shipped with ice packs or other temporary refrigeration. Capsules will be
dispensed to subjects in separate bottles in quantities sufficient to last until their next
appointment. Any unused capsules will be returned to the PI or research staff and sent to
the pharmacy for destruction in compliance with Children's regulations.

Subjects will be randomized to 2 g of DHA or matched placebo for 12 weeks. In order to
achieve this dose of DHA, subjects will receive 2 950 mg capsules twice a day. Subjects who
cannot tolerate the divided dose of 2000 mg per day will be discontinued from the study.

Although much of our knowledge of the pathophysiology of concussion comes from animal
models, it is believed that the mechanical trauma to the brain causes a sudden disruption in
the ionic balances, leading to an increase in calcium and an increase in glucose metabolism
as cells try to compensate for the potassium/calcium imbalance. This is followed by a period
of decreased glucose metabolism which may last up to 4 weeks in humans, resulting in
continued high levels of calcium which interfere with mitochondrial oxidative metabolism.
This decrease in mitochondrial oxidative metabolism appears to be biphasic, with improvement
seen at 2, followed by a decrease which bottoms out on day 5 and recovers around day 10.
Other important aspects of the concussive trauma include free radical production, initiation
of inflammatory responses, and altered neurotransmission.

DHA has several important functions in the brain with relatively few side effects, making it
a good option for concussion treatment. DHA is helpful in modulating ion channels; higher
levels of DHA are associated with higher levels of sodium pump activity, so it is possible
that providing DHA post-injury may help the cells reduce the calcium balance more quickly or
efficiently. DHA also has an apparent anti-inflammatory action. DHA interferes with the
inflammatory arachidonic acid cascade by reducing the affinity of platelet TxA2/PGH2
receptor for its ligand. Additionally, higher levels of DHA in the cerebral cortex cause
significantly higher levels of the anti-oxidant enzymes catalase, glutathione and
glutathione peroxidase -- resulting in decreased cerebral levels of lipid peroxides. DHA
reduces formation of the peroxynitrite free radical and reduces formation of
pro-inflammatory cytokines by inhibiting transcription factor NF−κB and inducible nitric
oxide synthetase. Finally, DHA is highly concentrated in synapses, indicating a role in
synaptic signal transduction. DHA appears to address many different aspects of how we
believe concussive injury affects the brain.

The primary outcomes of this feasibility trial are to determine the willingness of patients
to be randomized, the expected rate of enrollment based on the clinic population, and
protocol adherence of enrolled study participants. We anticipate the results from this study
will provide data to inform a larger randomized trial of DHA for the treatment of pediatric
sports concussion. Secondary outcomes are time to clearance to return to play (in days) and
improvement in balance, as assessed by the Balance Error Scoring System (BESS) which is a
component of the Sport Concussion Assessment Tool 3 (SCAT-3). Time to clearance to return to
play was chosen as a clinically significant measurement for medical professionals in the
sports medicine field. The investigators will determine clearance for return to full
competitive game play (Stage 6 of graduated return to play protocol) according to Consensus
Statement guidelines and following the law in Texas, House Bill 2038. Criteria for return to
play include complete clinical recovery from the concussion including returning to baseline
symptoms, exam and neurocognitive function and successful completion of a gradual return to
play progression. The BESS was chosen because it is a relatively simple assessment that has
been noted by the investigators to be a good predictor of neurological recovery.

In addition to time to return to play and the BESS, the SCAT-3 and Immediate Post Concussion
Assessment and Cognitive Testing (ImPACT) computerized neurocognitive testing programs will
be used to evaluate recovery. The SCAT-3 is a standardized method of evaluating injured
athletes for concussion and can be used in athletes aged from 10 years and older. The ImPACT
program is a computerized exam that helps to quantify the degree of symptom, injury, or
dysfunction that occurs after a sports related concussion. Although this test is utilized by
many professionals, college, and high school sports programs throughout the country, it is
unclear if its use contributes to a safer or more expedited return to activity.

Finally, information on side effects will be collected at every visit in order to track the
rate and severity of side effects in this patient population.

We plan to enroll 40 subjects for this study, which consists of 20 subjects to be treated
with DHA and 20 subjects to be treated with placebo. In order to achieve enrollment of 40
total subjects, we anticipate screening 80 subjects in order to consent 40. Because this is
a pilot study, information on early withdrawals is important to us and no extra subjects
will be consented due to this. We anticipate that it will take approximately 12 months to
complete enrollment, with an additional 3 months for patient follow-up once the last patient
has been enrolled. We anticipate that it will take approximately 6-9 months to complete data
clean-up, analysis, and manuscript submission for total study duration of 2 years.

Subjects who are non-compliant with the protocol either by not keeping appointments or by
not taking study pills as directed may be discontinued from the study. Subjects who do not
tolerate the minimum dose of 2000 mg of DHA per day or who experience intolerable side
effects will be discontinued. Subjects who choose to withdraw consent will be discontinued
early.

Participant Eligibility


Inclusion Criteria:

1. Male or females age 14-18 inclusive

2. Diagnosed with concussion due to sports-related injury. Concussion is defined as:

1. Direct blow to the head, face, neck or a blow elsewhere on the body with an
"impulsive" force transmitted to the head.

2. Rapid onset of short-lived impairment of neurologic function in one or more of
the following clinical domains that resolves spontaneously:

i. Symptoms: somatic (eg, headache), cognitive (eg, feeling like in a fog and/or
emotional symptoms (eg, lability).

ii. Physical signs (eg, loss of consciousness, amnesia).

iii. Behavioral changes (eg, irritability).

iv. Cognitive impairment (eg, slowed reaction times).

v. Sleep disturbance (eg, drowsiness). c) No abnormality on standard structural
neuroimaging studies, if such neuroimaging studies are completed for a
clinically-indicated reason. Note: neuroimaging is not a part of this study protocol.
Study participants will not undergo neuroimaging as part of this study.

3. Concussion within 4 days of enrollment

4. Presenting for treatment to the Sports Medicine Center at Children's Medical Center

Exclusion Criteria:

1. Subjects not actively participating in an organized sport at time of enrollment

2. Subjects who received a concussion from an event other than playing a sport (motor
vehicle accident, fall, etc.)

3. Subjects who participate in or received a concussion during participation in
motorized sports (i.e., motorcross, dirt biking, jet skiing, etc.)

4. Subjects with radiographic evidence of traumatic brain injury (i.e., skull fracture,
intracranial hemorrhage, cerebral contusion, etc).

5. Subjects with a prior diagnosed concussion in the previous 6 months.

6. Pregnant women.

7. Subjects sensitive to aspirin

8. Subjects diagnosed with high blood pressure and currently being treated with blood
pressure medications

9. Subjects allergic to soy bean oil or corn oil.

10. Subjects currently taking fish oil or DHA supplements.