Nutrition for Post-Traumatic Headache
Nutrition for Post-Traumatic Headache
The purpose of this multi-site study is to evaluate the efficacy of a high omega-3/low
 omega-6 dietary intervention (the H3-L6 Diet) vs. a Control Diet in reducing headache pain
 and improving function in soldiers, veterans and military healthcare beneficiaries with
 post-traumatic headache (PTH). In addition, the study will examine the effects of the diet
 interventions on anti-nociceptive and pro-nociceptive lipid mediators derived from omega-3
 and omega-6 fatty acids.
Migraine-like PTH is an ideal patient population to test the effects of the H3-L6
 intervention for several reasons. First, although PTH is considered a secondary headache
 syndrome, the fact that migraine-like PTH has a phenotype indistinguishable from primary
 migraine disorders and shares common pain-related comorbidities (e.g. anxiety, depression)
 suggests that shared biochemical mechanisms may underlie both conditions. Second, many PTH
 patients experience poor or incomplete therapeutic responses to available treatments, often
 while suffering from drug-related adverse effects. The prospect of improved headache outcomes
 with concurrent reduction in medication use (as seen in the Chronic Daily Headache Trial) may
 be particularly beneficial in PTH, since certain headache medications (e.g. opiates, muscle
 relaxants, sleep aids) have cognitive side effects, which may worsen residual cognitive
 impairment from Traumatic Brain Injury (TBI).

 While PTH is an important cause of disability after TBI, problems with memory, executive
 function, depression, anxiety, irritability, fatigue, post-traumatic stress, and other
 neurobehavioral disorders are also common after TBI and contribute to disability. The H3-L6
 (High Omega-3 Low Omega-6) intervention increased circulating concentrations of several key
 bioactive mediators which could hypothetically also have favorable effects on these
 TBI-associated non-headache impairments associated with TBI combat injuries. Omega-3 fatty
 acids have been widely studied in pre-clinical models and human TBI and demonstrate promising
 evidence of both neuroprotective and neurorestorative efficacy.

 Potential mechanisms include antioxidant, anti-inflammatory, and pro-neurogenic effects. In
 our pilot study, the H3-L6 intervention significantly increased circulating levels of
 docosahexaenoic acid-eicosapentaenoic acid (DHA-EPA) , a potent stimulator of neurite growth
 and synaptogenesis in hippocampus and other central nervous system (CNS) tissues.
 Corresponding increases in the synaptamide biosynthesis in central nervous system tissues
 could hypothetically assist cognitive and functional neurorecovery associated with traumatic
 brain injury. Further, the reduction of proinflammatory metabolites of omega-6 fatty acids
 may provide additional benefits beyond what can be achieved through omega-3 supplementation
 alone.

 Study Type: Interventional, Phase 2, double blind Study Design: Allocation: Randomized,
 parallel group Masking: Double Blind (Participant, Investigator, Outcomes Assessor) Primary
 Purpose: Treatment

 Primary Outcome Measures:

 Hypothesis and Objective: The investigators will obtain support for the following hypotheses
 through three specific aims:

 Specific Aim 1: To compare the efficacy of the H3-L6 Diet to the Control Diet, in reducing
 headache pain and improving headache-related quality of life.

 Hypothesis 1: Compared to the Control Diet, the H3-L6 Diet will produce significant
 improvement in:

 (1a) the Headache Impact Test-a headache-specific quality of life measure-Primary Clinical
 Outcome);

 (1b) mean total Headache Hours per day; and

 (1c) mean Severe Headache Hours per day.

 Secondary Outcomes Measures:

 Specific Aim 2: To evaluate whether the H3-L6 Diet can increase circulating anti-nociceptive
 omega-3 metabolites, and reduce pro-nociceptive omega-6 metabolites, in patients with
 Posttraumatic Headaches.

 Hypothesis 2: Compared to the Control Diet, the H3-L6 Diet will produce significant increases
 in anti-nociceptive omega-3 metabolites including 17-hydroxy DHA (Primary Biochemical Aim),
 and reductions in pro-nociceptive omega-6 metabolites.

 Other Outcomes Measures Specific Aim 3: To explore the potential of the H3-L6 intervention
 for improving non-headache TBI outcomes.

 Hypothesis 3: Compared to the Control Diet, the H3-L6 Diet will produce significant
 improvement in:

 (3a) non-headache pain; (3b) depression/anxiety; (3c) symptoms of post-traumatic stress
 disorder; (3d) cognitive function; (3e) sleep quality; and (3f) will significantly reduce the
 use of acute pain medications. Enrollment: Up to 300 total participants enrolled among the 3
 military sites for 120 12-week diet completers
Inclusion Criteria:

 -  In order to be included in the study, you must be a person of either gender who is at
 least 18 years of age, meets criteria of having had a traumatic brain injury, a
 physiological disruption of brain function, as manifested by at least one of the
 following:

 1. . Any period of loss of consciousness

 2. . Any loss of memory for events immediately before or after the accident

 3. . Any alteration of mental state at the time of the accident (e.g., feeling
 dazed, disoriented, and confused)

 4. . Focal neurologic deficits that may or may not be permanent.

 -  Traumatically induced includes the head being struck, the head striking an
 object, or the brain undergoing an acceleration/deceleration movement (i.e.
 whiplash) without direct external trauma to the head.

 -  Meets Internation Classification of Headache Disorders-version III (ICHD-III) criteria
 for persistent post-traumatic headache which is defined as a headache of at least 3
 months duration caused by a traumatic injury to the head.

 -  Meets ICHD-III criteria for episodic/chronic migraine, with or without aura (excepting
 exclusion for organic disease):

 1. . Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)

 2. . Headache has at least 2 of the following characteristics:

 1. unilateral location

 2. pulsating quality

 3. moderate or severe pain intensity

 4. aggravation by or causing avoidance of routine physical activity (eg,
 walking or climbing stairs)

 3. . During headache at least 1 of the following:

 1. nausea and/or vomiting

 2. photophobia and phonophobia

 -  A potential candidate for this study must be under the care of a physician for
 headaches and have an incomplete response to standard headache treatments.

 -  Must have headache frequency of more than 8 days per month.

 -  Must have a headache history of more than 6 months

 -  Must be able to attend or remotely participate (by video conference or telephone) in
 seven dietitian counseling sessions, and adhere to diet supplied to study
 participants.

 -  Must be a Department of Defense (DoD) healthcare beneficiary and eligible to receive
 care at Walter Reed National Military Medical Center (WRNMMC), Fort Belvoir Community
 Hospital (FBCH) or Womack Army Medical Center (WAMC).

 Exclusion Criteria:

 -  A person cannot be in this study if they have a history of specific food allergies,
 especially to fish, dairy or gluten.

 Also exclusionary are:

 -  Pregnancy or anticipated pregnancy

 -  Aversion to eating fish

 -  History of organic brain disorder other than TBI (vasculitis, encephalitis,
 meningitis, brain tumor)

 -  Major medical illness such as malignancy, diabetes, autoimmune or immune deficiency
 disorders, history of stroke or myocardial infarction

 -  Anticipated deployment or move to alternate location in the next 16 weeks

 -  Inability to read and communicate in English

 -  Regular use of fatty acid containing supplements

 -  Active or recent (2 years) history of treatment for substance abuse

 -  Cognitive impairment that prevents understanding of the protocol and completion of
 study procedures including compliance with the diet, blood draws and maintaining a
 daily headache diary.