{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:46:54Z","timestamp":1762429614403,"version":"build-2065373602"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["2024-2-4193"],"award-info":[{"award-number":["2024-2-4193"]}]},{"name":"2024 Post-Support Program for Cultivation of Topnotch Innovative Talents","award":["2024YTH0015"],"award-info":[{"award-number":["2024YTH0015"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Migraine, a leading global cause of disability, affects over 1.1 billion individuals worldwide. Current acute pharmacotherapy is limited by contraindications and adverse events (AEs), underscoring the need for safer, more effective alternatives. The Sishun Formula (SSF), a traditional Chinese medicine (TCM) formulation targeting \u201cYing-Wei disharmony,\u201d demonstrated promising preclinical and preliminary clinical results. This trial aims to rigorously evaluate SSF\u2019s efficacy and safety for acute migraine attacks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>This multicenter, randomized, double-blind, placebo-controlled trial will enroll 144 participants with acute migraine and \u201cYing-Wei disharmony\u201d syndrome, randomized 1:1 to SSF or placebo. A single dose of SSF or a matched placebo is administered within 0.5\u202fh of migraine onset. The primary outcome is the proportion achieving headache freedom at 2\u202fh post-dose. Secondary outcomes include the proportion achieving headache relief at 2\u202fh post-dose, absence of most bothersome associated symptoms, sustained relief\/freedom at 24\/48\u202fh, the Visual Analogue Scale (VAS) score changes, time to efficacy onset, recurrence rates, and TCM syndrome improvement. Biomarkers [e.g., calcitonin gene-related peptide (CGRP)] and safety parameters (vital signs, laboratory tests, AEs) are monitored. Data analysis will employ SPSS 25.0 and R 4.3.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings are anticipated to deliver high-quality evidence validating SSF\u2019s efficacy and safety, offering a promising therapeutic alternative for acute migraine attacks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>http:\/\/itmctr.ccebtcm.org.cn\/<\/jats:uri>\n                      , identifier ITMCTR2025000187.\n                    <\/jats:p>\n                  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