Targeted dietary interventions to reduce pain in persistent post-traumatic headache among service members: Protocol for a randomized, controlled parallel-group trial.

Ann Nothwehr, Kimbra Kenney, Christopher E Ramsden, J Douglas Mann, Chirayath Suchindran, Ramon Diaz-Arrastia, Ruth Clark, J Kent Werner, Cecily Jones, Katie Russell, Jacques Arrieux, Keturah R Faurot, Wanda Rivera, Olafur Palsson, Anthony F Domenichiello, Melissa Guerra, Brittney Roberson, Carol B Moore, Margaret Dunlap, Beth A MacIntosh, Wesley R Cole

Journal: Contemporary clinical trials 2022;119():106851

PMID: 35842107

Abstract

INTRODUCTION

Post-traumatic headache (PTH) is common after traumatic brain injury (TBI), especially among active-duty service members (SMs), affecting up to 35% of patients with chronic TBI. Persistent PTH is disabling and frequently unresponsive to treatment and is often migrainous. Here, we describe a trial assessing whether dietary modifications to increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduce n-6 linoleic acid (LA), will alter nociceptive lipid mediators and result in clinical improvements in persistent PTH.

METHODS

This prospective, randomized, controlled trial tests the efficacy, safety, and biochemical effects of targeted, controlled alterations in dietary n-3 and n-6 fatty acids in 122 adult SMs and military healthcare beneficiaries with diagnosed TBI associated with actively managed persistent frequent (>8 /month) PTH with migraine. Following a 4-week baseline, participants are randomized to one of two equally intensive dietary regimens for 12 additional weeks: 1) increased n-3 EPA + DHA with low n-6 LA (H3L6); 2) usual US dietary content of n-3 and n-6 fatty acids (Control). During the intervention, participants receive diet arm-specific study oils and foods sufficient for 75% of caloric needs and comprehensive dietary counseling. Participants complete daily headache diaries throughout the intervention. Clinical outcomes, including the Headache Impact Test (HIT-6), headache hours per day, circulating blood fatty acid levels, and bioactive metabolites, are measured pre-randomization and at 6 and 12 weeks. Planned primary analyses include pre-post comparisons of treatment groups on clinical measures using ANCOVA and mixed-effects models. Similar approaches to explore biochemical and exploratory clinical outcomes are planned.

CLINICALTRIALS

gov registration: NCT03272399.

Copyright © 2022 Elsevier Inc. All rights reserved.

Address: Department of Physical Medicine & Rehabilitation, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America. Electronic address: [email protected].; Department of Brain Injury Medicine, Intrepid Spirit Center, Womack Army Medical Center, Fort Bragg, NC, United States of America; Matthew Gfeller Center, Department of Exercise and Sport Science, the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.; Metabolic and Nutrition Research Core, University of North Carolina Health, Chapel Hill, NC, United States of America.; Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America; National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States of America; Traumatic Brain Injury Clinic, Neurology Department, Fort Belvoir Community Hospital, Fort Belvoir, VA, United States of America.; Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.; Department of Physical Medicine & Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America; The Geneva Foundation, Bethesda, MD, United States of America.; Department of Physical Medicine and Rehabilitation, South Texas Veterans Healthcare System, San Antonio, TX, United States of America.; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States of America.; Department of Medicine, the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.; Traumatic Brain Injury Clinic, Neurology Department, Fort Belvoir Community Hospital, Fort Belvoir, VA, United States of America; Intrepid Spirit Center, Fort Belvoir Community Hospital, Fort Belvoir, VA, United States of America; Department of Neurology, Fort Belvoir Community Hospital, Fort Belvoir, VA, United States of America.; National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States of America.; Department of Brain Injury Medicine, Intrepid Spirit Center, Womack Army Medical Center, Fort Bragg, NC, United States of America.; Jack, Joseph, and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, Cleveland, OH, United States of America.; Kent State University, Kent, OH, United States of America.; Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America; National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States of America.; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States of America.; Department of Biostatistics, Gillings School of Global Public Health, the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.; Department of Neurology, the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States of America; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States of America.
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