Nutrition for Post-Traumatic Headache

NCT ID: NCT03272399

Last Updated: 2021-10-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-21
• Study Completion Date: 2022-03-31

Brief Summary

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.

Detailed Description

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

Conditions

Post-Traumatic Headache Chronic Without Intractable Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

H3-L6

High Omega-3, low Omega-6 diet

Group Type: EXPERIMENTAL

Diet/nutrition intervention

Intervention Type: OTHER

The intervention will be administered through food products rather than dietary supplements

L3-H6

Control diet containing average US polyunsaturated fatty acid (PUFA) content with low omega-3 and high omega-6 content

Group Type: ACTIVE_COMPARATOR

Diet/nutrition intervention

Intervention Type: OTHER

The intervention will be administered through food products rather than dietary supplements

Interventions

Diet/nutrition intervention

The intervention will be administered through food products rather than dietary supplements

Intervention Type: OTHER

Other Intervention Names

High omega-3 versus high omega-6 dietary intervention

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Walter Reed National Military Medical Center

FED

Sponsor Role: collaborator

Fort Belvoir Community Hospital

FED

Sponsor Role: collaborator

Womack Army Medical Center

FED

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Uniformed Services University of the Health Sciences

FED

Sponsor Role: lead

Responsible Party

Kimbra Kenney

Associate Professor, Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kimbra Kenney, MD

Role: PRINCIPAL_INVESTIGATOR

Uniformed Services University of the Health Sciences

Chris Ramsden, MD

Role: STUDY_DIRECTOR

National Institutes of Health (NIH)

John Mann, MD

Role: STUDY_DIRECTOR

UNC

Locations

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Womack Army Medical Center (WAMC)

Fort Bragg, North Carolina, United States

Site Status: RECRUITING

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kimbra Kenney, MD

Role: CONTACT

kimbra.kenney@usuhs.edu

301 400 0492

Carol Moore, MS

Role: CONTACT

carol.moore.ctr@usuhs.edu

Facility Contacts

Cora Davis

Role: primary

cora.davis.ctr@usuhs.edu

301-319-3780

Kimbra Kenney, MD

Role: backup

kimbra.kenney@usuhs.edu

301 400 0942

Jacques Arrieux

Role: primary

jacques.p.arrieux.ctr@mail.mil

910-908-2268

Katie Russell

Role: backup

katie.n.russell.ctr@mail.mil

910 908 2274

Rebecca Sandlain

Role: primary

rebecca.l.sandlain.ctr@mail.mil

Melissa Guerra, MD

Role: backup

melissa.f.guerra.civ@mail.mil

References

Ramsden CE, Faurot KR, Zamora D, Suchindran CM, MacIntosh BA, Gaylord S, Ringel A, Hibbeln JR, Feldstein AE, Mori TA, Barden A, Lynch C, Coble R, Mas E, Palsson O, Barrow DA, Mann DJ. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Pain. 2013 Nov;154(11):2441-2451. doi: 10.1016/j.pain.2013.07.028. Epub 2013 Jul 22.

Reference Type: BACKGROUND

PMID: 23886520 (View on PubMed)

Ramsden CE, Faurot KR, Zamora D, Palsson OS, MacIntosh BA, Gaylord S, Taha AY, Rapoport SI, Hibbeln JR, Davis JM, Mann JD. Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache: a secondary analysis of a randomized trial. Pain. 2015 Apr;156(4):587-596. doi: 10.1097/01.j.pain.0000460348.84965.47.

Reference Type: BACKGROUND

PMID: 25790451 (View on PubMed)

Faurot KR, Cole WR, MacIntosh BA, Dunlap M, Moore CB, Roberson B, Guerra M, Domenichiello AF, Palsson O, Rivera W, Nothwehr A, Arrieux J, Russell K, Jones C, Werner JK, Clark R, Diaz-Arrastia R, Suchindran C, Mann JD, Ramsden CE, Kenney K. Targeted dietary interventions to reduce pain in persistent post-traumatic headache among service members: Protocol for a randomized, controlled parallel-group trial. Contemp Clin Trials. 2022 Aug;119:106851. doi: 10.1016/j.cct.2022.106851. Epub 2022 Jul 13.

Reference Type: DERIVED

PMID: 35842107 (View on PubMed)

Related Links

http://www.medlineplus.gov/traumaticbraininjury.html

Medline Plus related topic: Traumatic Brain Injury

http://www.medlineplus.gov/headache.html

Medline Plus related topic: Post-traumatic headache

http://www.medlineplus.gov/migraine.html

Medline Plus related topic: Migraine

Other Identifiers

416047

Identifier Type: -

Identifier Source: org_study_id