Omega-3 Supplementation with Lipid Biomarker Assessment in Youth with Migraine: A Quasi-Randomized Controlled Feasibility Trial
- 1University of North Carolina, Chapel Hill
Abstract
BackgroundOmega-3 polyunsaturated fatty acids may modulate lipid-mediated inflammatory pathways implicated in migraine, yet pediatric trial methodologies evaluating biologic target engagement remain limited. This study evaluated the feasibility of conducting a pediatric nutrition-based migraine intervention trial integrating longitudinal dried blood spot biomarker collection, validated patient-reported outcome measures, dietary assessment, and caregiver-reported acceptability measures.
MethodsA quasi-randomized, double-blind, placebo-controlled feasibility trial was conducted at two academic pediatric neurology clinics. Children and adolescents aged 10-17 years with migraine were assigned 1:1 using sequential alternating allocation to daily omega-3 supplementation (850 mg eicosapentaenoic acid + docosahexaenoic acid) or matched coconut oil placebo for 12 weeks. Feasibility outcomes included recruitment yield, participant retention, caregiver-reported supplement adherence, dried blood spot biospecimen completion, 24-hour dietary recall completion, and intervention acceptability assessed via caregiver exit questionnaire. Feasibility benchmarks were established post hoc based on published pediatric trial literature: recruitment >70% of target sample, retention [≥]70%, supplement adherence [≥]70% of caregivers reporting administration on most days, biospecimen completion [≥]90%, dietary recall completion [≥]80%, and acceptability rated favorably by [≥]70% of caregivers. Clinical efficacy outcomes will be reported separately.
ResultsOf 58 individuals assessed for eligibility, 57 were enrolled and allocated (29 intervention, 28 placebo). Forty-four participants (77%) completed the 12-week follow-up (22 per group), meeting the retention benchmark. Dried blood spot collection was completed at both time points for all participants who attended study visits (100%). All 44 study completers finished all four planned dietary recalls (100% completion). Caregiver-reported acceptability was high, with the majority rating daily supplement administration as acceptable and reporting openness to future dietary supplement use for migraine management. Thirteen participants discontinued: five withdrew, five were lost to follow-up, two discontinued due to supplement palatability, and one no longer met inclusion criteria. Structured telephone follow-up at weeks 4 and 8 supported retention and adherence monitoring.
ConclusionsThis feasibility trial demonstrated that a pediatric nutrition-based migraine intervention integrating dried blood spot biomarker collection, repeated dietary recalls, validated patient-reported outcomes, and structured remote follow-up is feasible and acceptable to families. All six post-hoc feasibility benchmarks were met. Findings support progression to a larger-scale randomized controlled trial with modifications including concealed randomization, prospective daily headache diaries, and longer intervention duration.
Trial registrationClinicalTrials.gov, NCT06899074. Registered 20 March 2025.
Key Messages Regarding FeasibilityO_ST_ABS1) What uncertainties existed regarding the feasibility?C_ST_ABSIt was uncertain whether children and adolescents with migraine could be successfully recruited from multiple pediatric neurology clinics, whether families would adhere to daily liquid supplementation over 12 weeks, and whether longitudinal dried blood spot biospecimen collection, repeated telephone-administered dietary recalls, and multidimensional patient-reported outcome assessment could be feasibly integrated within a pediatric outpatient research setting.
2) What are the key feasibility findings?Retention was 77% (44/57), caregiver-reported supplement adherence met the [≥]70% threshold, biospecimen and dietary recall completion rates were 100% among study completers, and caregiver-reported acceptability was rated at least moderately acceptable by 96% of study completers. All feasibility benchmarks were met, supporting the overall viability of the study framework. Supplement palatability and disruptions to daily routine were the most commonly reported adherence challenges.
3) What are the implications of the feasibility findings for the design of the main study?A future definitive trial is warranted and should incorporate concealed computer-generated randomization, prospective daily electronic headache diaries as the primary clinical endpoint, longer intervention duration ([≥]16 weeks), consideration of higher omega-3 doses informed by predictive modeling of omega-3 index response, objective adherence monitoring, expanded lipid biomarker panels, and targeted recruitment strategies to improve demographic diversity.
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BibTeX
@misc{bain2026omega3,
title = {{Omega-3 Supplementation with Lipid Biomarker Assessment in Youth with Migraine: A Quasi-Randomized Controlled Feasibility Trial}},
author = {J. Bain and D. Zamora and K. R. Faurot and S. R. Shaikh and A. E. Sanders and S. Glover and K. Werner and S. P. Trau and K. Divaris and C. M. Sawicki},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.26362637},
url = {https://www.medrxiv.org/content/10.64898/2026.09.09.26362637v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Omega-3 Supplementation with Lipid Biomarker Assessment in Youth with Migraine: A Quasi-Randomized Controlled Feasibility Trial
AU - J. Bain
AU - D. Zamora
AU - K. R. Faurot
AU - S. R. Shaikh
AU - A. E. Sanders
AU - S. Glover
AU - K. Werner
AU - S. P. Trau
AU - K. Divaris
AU - C. M. Sawicki
PY - 2026
DA - 2026/09/09
PB - medRxiv
DO - 10.64898/2026.09.09.26362637
UR - https://www.medrxiv.org/content/10.64898/2026.09.09.26362637v1
AB - BackgroundOmega-3 polyunsaturated fatty acids may modulate lipid-mediated inflammatory pathways implicated in migraine, yet pediatric trial methodologies evaluating biologic target engagement remain limited. This study evaluated the feasibility of conducting a pediatric nutrition-based migraine intervention trial integrating longitudinal dried blood spot biomarker collection, validated patient-reported outcome measures, dietary assessment, and caregiver-reported acceptability measures. MethodsA quasi-randomized, double-blind, placebo-controlled feasibility trial was conducted at two academic pediatric neurology clinics. Children and adolescents aged 10-17 years with migraine were assigned 1:1 using sequential alternating allocation to daily omega-3 supplementation (850 mg eicosapentaenoic acid + docosahexaenoic acid) or matched coconut oil placebo for 12 weeks. Feasibility outcomes included recruitment yield, participant retention, caregiver-reported supplement adherence, dried blood spot biospecimen completion, 24-hour dietary recall completion, and intervention acceptability assessed via caregiver exit questionnaire. Feasibility benchmarks were established post hoc based on published pediatric trial literature: recruitment >70% of target sample, retention [≥]70%, supplement adherence [≥]70% of caregivers reporting administration on most days, biospecimen completion [≥]90%, dietary recall completion [≥]80%, and acceptability rated favorably by [≥]70% of caregivers. Clinical efficacy outcomes will be reported separately. ResultsOf 58 individuals assessed for eligibility, 57 were enrolled and allocated (29 intervention, 28 placebo). Forty-four participants (77%) completed the 12-week follow-up (22 per group), meeting the retention benchmark. Dried blood spot collection was completed at both time points for all participants who attended study visits (100%). All 44 study completers finished all four planned dietary recalls (100% completion). Caregiver-reported acceptability was high, with the majority rating daily supplement administration as acceptable and reporting openness to future dietary supplement use for migraine management. Thirteen participants discontinued: five withdrew, five were lost to follow-up, two discontinued due to supplement palatability, and one no longer met inclusion criteria. Structured telephone follow-up at weeks 4 and 8 supported retention and adherence monitoring. ConclusionsThis feasibility trial demonstrated that a pediatric nutrition-based migraine intervention integrating dried blood spot biomarker collection, repeated dietary recalls, validated patient-reported outcomes, and structured remote follow-up is feasible and acceptable to families. All six post-hoc feasibility benchmarks were met. Findings support progression to a larger-scale randomized controlled trial with modifications including concealed randomization, prospective daily headache diaries, and longer intervention duration. Trial registrationClinicalTrials.gov, NCT06899074. Registered 20 March 2025. Key Messages Regarding FeasibilityO_ST_ABS1) What uncertainties existed regarding the feasibility?C_ST_ABSIt was uncertain whether children and adolescents with migraine could be successfully recruited from multiple pediatric neurology clinics, whether families would adhere to daily liquid supplementation over 12 weeks, and whether longitudinal dried blood spot biospecimen collection, repeated telephone-administered dietary recalls, and multidimensional patient-reported outcome assessment could be feasibly integrated within a pediatric outpatient research setting. 2) What are the key feasibility findings?Retention was 77% (44/57), caregiver-reported supplement adherence met the [≥]70% threshold, biospecimen and dietary recall completion rates were 100% among study completers, and caregiver-reported acceptability was rated at least moderately acceptable by 96% of study completers. All feasibility benchmarks were met, supporting the overall viability of the study framework. Supplement palatability and disruptions to daily routine were the most commonly reported adherence challenges. 3) What are the implications of the feasibility findings for the design of the main study?A future definitive trial is warranted and should incorporate concealed computer-generated randomization, prospective daily electronic headache diaries as the primary clinical endpoint, longer intervention duration ([≥]16 weeks), consideration of higher omega-3 doses informed by predictive modeling of omega-3 index response, objective adherence monitoring, expanded lipid biomarker panels, and targeted recruitment strategies to improve demographic diversity.
ER -