Post-Traumatic Headache Chronic Without Intractable HeadachePhase 2NCT03272399
Nutrition for Post-Traumatic Headache
A Phase 2 study testing Diet/nutrition intervention in people with Post-Traumatic Headache Chronic Without Intractable Headache, run by Uniformed Services University of the Health Sciences at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-Traumatic Headache Chronic Without Intractable Headache
- What is being tested?
- Diet/nutrition intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Aug 2017to 31 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- . Any period of loss of consciousness
- . Any loss of memory for events immediately before or after the accident
- . Any alteration of mental state at the time of the accident (e.g., feeling dazed, disoriented, and confused)
- . 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.
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- 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):
- . Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
- . Headache has at least 2 of the following characteristics:
- unilateral location
- pulsating quality
- moderate or severe pain intensity
- aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)
- . During headache at least 1 of the following:
- nausea and/or vomiting
- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country.
Carol Moore, MS contact
United States3 sites, 3 recruiting
- Recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
Cora Davis, 301-319-3780, cora.davis.ctr@usuhs.edu
Kimbra Kenney, MD, 301 400 0942, kimbra.kenney@usuhs.edu
- Recruiting
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, 22060
Rebecca Sandlain, rebecca.l.sandlain.ctr@mail.mil
Melissa Guerra, MD, melissa.f.guerra.civ@mail.mil
- Recruiting
Womack Army Medical Center (WAMC)
Fort Bragg, North Carolina, 28310
Jacques Arrieux, 910-908-2268, jacques.p.arrieux.ctr@mail.mil
Katie Russell, 910 908 2274, katie.n.russell.ctr@mail.mil
About this study
Official title: Targeted Alteration in Omega-3 and Omega-6 Fatty Acids for Post-traumatic Headache (Nutrition for PTH)
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.
Read the 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
- Being tested
- Diet/nutrition intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diet/nutrition interventionOther
Also called High omega-3 versus high omega-6 dietary intervention
The intervention will be administered through food products rather than dietary supplements
| Study group | Role | What they receive |
|---|---|---|
| H3-L6 | Experimental | High Omega-3, low Omega-6 diet Receives: Other: Diet/nutrition intervention |
| L3-H6 | Active comparator | Control diet containing average US polyunsaturated fatty acid (PUFA) content with low omega-3 and high omega-6 content Receives: Other: Diet/nutrition intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Clinical Outcome: To compare the efficacy of the high omega-3/low omega-6 (H3-L6) diet to the low omega-3/high omega-6 (L3-H6) diet in reducing headache pain and improving headache-related quality of life.
Up to 300 participants complete the Headache Impact Test (HIT-6)-a headache-specific quality of life measure 6 times while enrolled in the study. The primary outcome measure is the change in the HIT-6 scores at baseline and at the end of the diet intervention.
Measured: The HIT-6 is administered at study visits at week 0 (enrollment), 4, 10, 12, 14, 16
Primary Biochemical Outcome: To evaluate the effects of the H3-L6 and L3-H6 Diet on circulating fatty acids and bioactive metabolites.
All study participants will have blood drawn 3 times during the 16-week study for analysis of circulating fatty acids and their bioactive metabolites. The following fatty acids will be measured in each blood sample (ng or pg per mL): 17-hydroxy-DHA (docosahexaenoic acid), 18-Hydroxy-EPA (eicosapentaenoic acid), 9-HODE (hydroxyl-octadecadienoic acid), 13-ODE (octadecadienoic acid), 5-HETE (hydroxyl-eicosatetraenoic acid), 8-HETE, 9-HETE, 11-HETE. Changes in 17-hydroxy-DHA and related fatty acids levels between blood draws at baseline and at the end of the 12-week diet intervention will be compared with changes in headache frequency and severity at the same time points.
Measured: Fasting blood draws at study visits at weeks 4, 10, 16
Secondary outcomes (7)
To compare the efficacy of the high omega-3/low omega-6 (H3-L6) diet to the low omega-3/high omega-6 (L3-H6) diet in reducing headache pain.
Up to 300 participants complete a headache diary daily while enrolled in the 16-week study. Participants record the total number of headache hours per day. The outcome measure is the change in the mean daily headache hours at baseline and at the end of the diet intervention between the H3-L6 and L3-H6 diet intervention groups.
Measured: Daily on-line diary entry during the 16-week study
To explore the potential of the H3-L6 intervention for improving non-headache pain outcomes.
Compared to the Control Diet, the H3-L6 Diet may produce significant improvement in non-headache pain. A survey of pain, the Total Body Pain Scale, will be administered at baseline and at the end of the 12-week diet intervention. The outcome measure is a reduction in non-headache pain as measured by the survey at baseline and at the end of the diet intervention.
Measured: Study visits at week 0 and 16
To explore the potential of the H3-L6 intervention for decreasing acute pain medication usage
Compared to the Control Diet, the H3-L6 Diet may produce significant improvement in: Use of acute pain medications. Participants will daily record all pain medications used in that 24-hour period. The outcome measure is the change in the acute pain medications sued at baseline and at the end of the diet intervention between the H3-L6 and L3-H6 diet intervention groups.
Measured: Daily on-line diary entry during the 16-week study
To explore the potential of the H3-L6 intervention for improving sleep quality
Compared to the Control Diet, the H3-L6 Diet may produce significant improvement in sleep quality. A sleep quality survey, the PSQI, will be administered at baseline at and the end of the 12-week diet intervention. The outcome measure is the change in the PSQI score at baseline and at the end of the diet intervention between the H3-L6 and L3-H6 diet intervention groups.
Measured: the PSQI is administered at weeks 4 and 16 of the study
To explore the potential of the H3-L6 intervention for improving psychological distress (depression/anxiety)
The PROMIS-29, a survey of psychological distress (depression/anxiety), will be administered at baseline and at the end of the 12-week diet intervention. The outcome measure is a reduction in depression and/or anxiety as measured by the PROMIS-29 at baseline and at the end of the diet intervention.
Measured: Study visits at week 0 and 16
To explore the potential of the H3-L6 intervention for improving symptoms of post-traumatic stress disorder (PTSD)
Compared to the Control Diet, the H3-L6 Diet may produce significant improvement in symptoms of post-traumatic stress disorder (PTSD). The PCL-C, a survey of post-traumatic stress symptoms, will be administered at baseline and at the end of the 12-week diet intervention. The outcome measure is the reduction in the PCL-C score at baseline and at the end of the diet intervention between the H3-L6 and L3-H6 diet intervention groups.
Measured: The PCL-C is administered at study visits at weeks 4 &16
To explore the potential of the H3-L6 intervention for improving post-concussive symptoms.
Compared to the Control Diet, the H3-L6 Diet may produce significant improvement in post-concussive symptoms. The Neurobehavioral Symptom Inventory (NSI) and the Glasgow Outcome Score-Extended (GOS-E) will be administered at baseline and at the end of the 12-week diet intervention. The outcome measure is a change in the NSI and GOS-E score at baseline and at the end of the diet intervention between the H3-L6 and L3-H6 diet intervention groups.
Measured: NSI and GOS-E are administered at weeks 4 and 16.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2017
- Study start21 Aug 2017
- Primary completion31 Mar 2022 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Post-Traumatic Headache Chronic Without Intractable HeadacheStudies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uniformed Services University of the Health Sciences
- Sponsor type
- US federal agency
- Collaborators
- Walter Reed National Military Medical Center, Fort Belvoir Community Hospital, Womack Army Medical Center, University of North Carolina, Chapel Hill, National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Kimbra Kenney, Uniformed Services University of the Health Sciences
- Investigators
- Kimbra Kenney, MD, Principal investigator, Uniformed Services University of the Health SciencesChris Ramsden, MD, Study director, National Institutes of Health (NIH)John Mann, MD, Study director, UNC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03272399
- Sponsor's protocol ID
- 416047
- Status last verified
- Oct 2021
- First submitted
- 21 Aug 2017
- Last updated
- 5 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study data to be uploaded into Federation Interagency Traumatic Brain Injury Repository (FITBIR) and made accessible after study is completed
Publications
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.
PubMed 23886520Ramsden 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.
PubMed 25790451Faurot 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.
PubMed 35842107
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Alteration in Omega-3 and Omega-6 Fatty Acids for Post-traumatic Headache (Nutrition for PTH)
- ClinicalTrials.gov ID
- NCT03272399
- Acronym / sponsor ID
- 416047
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Uniformed Services University of the Health SciencesUS federal agency
- Collaborators
- Walter Reed National Military Medical Center, Fort Belvoir Community Hospital, Womack Army Medical Center, University of North Carolina, Chapel Hill, National Institutes of Health (NIH)
- Study start
- 21 Aug 2017 (actual)
- Primary completion
- 31 Mar 2022 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 5 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H3-L6 | Experimental | Other: Diet/nutrition interventionHigh Omega-3, low Omega-6 diet |
| L3-H6 | Active comparator | Other: Diet/nutrition interventionControl diet containing average US polyunsaturated fatty acid (PUFA) content with low omega-3 and high omega-6 content |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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):
- 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.
Key exclusion criteria (11 listed)
- A person cannot be in this study if they have a history of specific food allergies, especially to fish, dairy or gluten.
- 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
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 |
|---|---|---|
| Diet/nutrition interventionAlso: High omega-3 versus high omega-6 dietary interventionThe intervention will be administered through food products rather than dietary supplements | Other | H3-L6, L3-H6 |
Primary outcome
Primary Clinical Outcome: To compare the efficacy of the high omega-3/low omega-6 (H3-L6) diet to the low omega-3/high omega-6 (L3-H6) diet in reducing headache pain and improving headache-related quality of life.
Time frame: The HIT-6 is administered at study visits at week 0 (enrollment), 4, 10, 12, 14, 16
Up to 300 participants complete the Headache Impact Test (HIT-6)-a headache-specific quality of life measure 6 times while enrolled in the study. The primary outcome measure is the change in the HIT-6 scores at baseline and at the end of the diet intervention.
Primary Biochemical Outcome: To evaluate the effects of the H3-L6 and L3-H6 Diet on circulating fatty acids and bioactive metabolites.
Time frame: Fasting blood draws at study visits at weeks 4, 10, 16
All study participants will have blood drawn 3 times during the 16-week study for analysis of circulating fatty acids and their bioactive metabolites. The following fatty acids will be measured in each blood sample (ng or pg per mL): 17-hydroxy-DHA (docosahexaenoic acid), 18-Hydroxy-EPA (eicosapentaenoic acid), 9-HODE (hydroxyl-octadecadienoic acid), 13-ODE (octadecadienoic acid), 5-HETE (hydroxyl-eicosatetraenoic acid), 8-HETE, 9-HETE, 11-HETE. Changes in 17-hydroxy-DHA and related fatty acids levels between blood draws at baseline and at the end of the 12-week diet intervention will be compared with changes in headache frequency and severity at the same time points.
7 secondary outcomes
To compare the efficacy of the high omega-3/low omega-6 (H3-L6) diet to the low omega-3/high omega-6 (L3-H6) diet in reducing headache pain.
Time frame: Daily on-line diary entry during the 16-week study
To explore the potential of the H3-L6 intervention for improving non-headache pain outcomes.
Time frame: Study visits at week 0 and 16
To explore the potential of the H3-L6 intervention for decreasing acute pain medication usage
Time frame: Daily on-line diary entry during the 16-week study
To explore the potential of the H3-L6 intervention for improving sleep quality
Time frame: the PSQI is administered at weeks 4 and 16 of the study
To explore the potential of the H3-L6 intervention for improving psychological distress (depression/anxiety)
Time frame: Study visits at week 0 and 16
To explore the potential of the H3-L6 intervention for improving symptoms of post-traumatic stress disorder (PTSD)
Time frame: The PCL-C is administered at study visits at weeks 4 &16
To explore the potential of the H3-L6 intervention for improving post-concussive symptoms.
Time frame: NSI and GOS-E are administered at weeks 4 and 16.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
- Background: PubMed 23886520Ramsden 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.
- Background: PubMed 25790451Ramsden 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.
- Derived from this study: PubMed 35842107Faurot 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.
- Medline Plus related topic: Traumatic Brain InjuryLink provided by the sponsor.
- Medline Plus related topic: Post-traumatic headacheLink provided by the sponsor.
- Medline Plus related topic: MigraineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Study data to be uploaded into Federation Interagency Traumatic Brain Injury Repository (FITBIR) and made accessible after study is completed
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.
Carol Moore, MS contact
Kimbra Kenney, MD principal investigator
Uniformed Services University of the Health Sciences
Chris Ramsden, MD study director
National Institutes of Health (NIH)
John Mann, MD study director
UNC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diet/nutrition intervention in people with Post-Traumatic Headache Chronic Without Intractable Headache, run by Uniformed Services University of the Health Sciences at 3 sites 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 22 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: status not confirmed, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kimbra Kenney, MD (301 400 0492, kimbra.kenney@usuhs.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Clinical Outcome: To compare the efficacy of the high omega-3/low omega-6 (H3-L6) diet to the low omega-3/high omega-6 (L3-H6) diet in reducing headache pain and improving headache-related quality of life. (time frame: The HIT-6 is administered at study visits at week 0 (enrollment), 4, 10, 12, 14, 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03272399, which also lists 3 linked publications.
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 5 Oct 2021.