NCT03272399

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2017

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 21, 2017

Completed
Same day until next milestone

Study Start

First participant enrolled

August 21, 2017

Completed
15 days until next milestone

First Posted

Study publicly available on registry

September 5, 2017

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2022

Completed
Last Updated

October 5, 2021

Status Verified

October 1, 2021

Enrollment Period

4.6 years

First QC Date

August 21, 2017

Last Update Submit

October 4, 2021

Conditions

Post-Traumatic Headache Chronic Without Intractable Headache

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    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.

    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.

    Study visits at week 0 and 16

  • To explore the potential of the H3-L6 intervention for decreasing acute pain medication usage

    Daily on-line diary entry during the 16-week study

  • To explore the potential of the H3-L6 intervention for improving sleep quality

    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)

    Study visits at week 0 and 16

  • +2 more secondary outcomes

Study Arms (2)

H3-L6

EXPERIMENTAL

High Omega-3, low Omega-6 diet

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

Other: Diet/nutrition intervention

Interventions

Diet/nutrition interventionOTHER

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

Also known as: High omega-3 versus high omega-6 dietary intervention
H3-L6L3-H6

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • 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
  • +6 more criteria

You may not qualify if:

  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

RECRUITING

Womack Army Medical Center (WAMC)

Fort Bragg, North Carolina, 28310, United States

RECRUITING

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

RECRUITING

Related Publications (3)

  • 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.

    PMID: 23886520BACKGROUND

  • 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.

    PMID: 25790451BACKGROUND

  • 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.

    PMID: 35842107DERIVED

Related Links

Study Officials

  • Kimbra Kenney, MD

    Uniformed Services University of the Health Sciences

    PRINCIPAL INVESTIGATOR

  • Chris Ramsden, MD

    National Institutes of Health (NIH)

    STUDY DIRECTOR

  • John Mann, MD

    UNC

    STUDY DIRECTOR

Central Study Contacts

Kimbra Kenney, MD

CONTACT

301 400 0492kimbra.kenney@usuhs.edu

Carol Moore, MS

CONTACT

carol.moore.ctr@usuhs.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor, Neurology

Study Record Dates

First Submitted

August 21, 2017

First Posted

September 5, 2017

Study Start

August 21, 2017

Primary Completion

March 31, 2022

Study Completion

March 31, 2022

Last Updated

October 5, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

Study data to be uploaded into Federation Interagency Traumatic Brain Injury Repository (FITBIR) and made accessible after study is completed

Shared Documents
STUDY PROTOCOL, CSR
Time Frame
After study is uploaded into FITBIR
Access Criteria
Through FITBIR

Locations

US(3)