{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:40:16Z","timestamp":1792669216892,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>According to estimates from the 2019 Global Burden of Disease (GBD) study, approximately 1.1 billion people worldwide suffer from migraine, with a prevalence rate of about 14% to 15%. Despite the development of various medications for different types of migraine, such as acetaminophen and caffeine combination preparations, most patients still experience suboptimal symptom control. Therefore, identifying effective and safer alternative treatments holds significant clinical importance. Acupuncture was formally recommended by the World Health Organization as a migraine therapy as early as 1979. In recent years, substantial domestic and international research evidence has demonstrated the distinct advantages of acupuncture in treating migraine. Proteomics technology can assess the final products of adaptive changes in the body following acupuncture, thereby establishing a close association with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to evaluate the efficacy of a single acupuncture session for acute migraine, identify subgroups with different short-term treatment responses, and explore baseline plasma protein biomarkers potentially associated with acupuncture response. An exploratory proof-of-concept model will be developed to assess whether a small set of prespecified clinical and proteomic features may contain preliminary predictive information regarding short-term treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is divided into three parts. First, this randomized controlled trial will recruit 86 acute migraine patients. All participants will be randomly assigned in a 1:1 ratio to either the real acupuncture (RA) group or the sham acupuncture (SA) group. Each patient will receive one acupuncture treatment session. The primary outcome is the between-group difference in the change in visual analog scale (VAS) scores from baseline to 24\u2005h post-treatment. Secondary outcomes include assessment of VAS scores at 72\u2005h and 1 week post-needling; Hamilton Anxiety Scale\/Hamilton Depression Scale (HAMA\/HAMD) at 1 week post-needling; clinical response rates at 24\u2005h, 72\u2005h, and 1 week post-needling; and migraine attack count, attack frequency, and attack duration at 24\u2005h, 72\u2005h, and 1 week post-needling. Second, using the prespecified percentage change in VAS as the efficacy metric, 20 participants will be selected from the 43 participants in the RA group, including 10 high-responders and 10 low-responders. Baseline plasma samples collected before acupuncture will be analyzed using DIA-based proteomics to identify differentially expressed proteins and explore biological pathways potentially associated with short-term acupuncture response. Third, an exploratory proof-of-concept treatment-response model will be developed using the clinical and proteomic data from these 20 participants. Because of the limited sample size, no training-test split will be performed and complex machine-learning algorithms will not be compared. A parsimonious penalized logistic regression model will be assessed using nested leave-one-out cross-validation, with all data-dependent preprocessing and feature-selection procedures performed within each resampling iteration. The results will be considered hypothesis-generating and will require independent external validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This protocol describes a randomized, single-blind trial that will evaluate the efficacy of acupuncture for acute migraine and explore plasma protein biomarkers potentially associated with short-term acupuncture response. The exploratory model is intended to assess methodological feasibility and generate hypotheses rather than provide a validated clinical decision-support tool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>www.chictr.org.cn<\/jats:ext-link>\n                      , identifier ITMCTR2026000359.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1939184","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:41:01Z","timestamp":1790001661000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and exploratory treatment-response modeling of acupuncture for acute migraine based on DIA proteomics: a study protocol for a randomized controlled trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"BeiJing Daxing District Hospital of Integrated Chinese and Western Medicine","place":["BeiJing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"BeiJing Daxing District Hospital of Integrated Chinese and Western Medicine","place":["BeiJing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailun","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","first-page":"881","article-title":"Chinese guidelines for the diagnosis and treatment of migraine (2022 edition)","volume":"28","year":"2022","journal-title":"Chin J Pain Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41582-022-00763-1","article-title":"Global epidemiology of migraine and its implications for public health and health policy","volume":"19","author":"Steiner","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/ene.15103","article-title":"Aspirin, paracetamol (Acetaminophen) and caffeine for the treatment of acute migraine attacks: a systematic review and meta-analysis of randomized placebo-controlled trials","volume":"29","author":"Diener","year":"2022","journal-title":"Eur J Neurol"},{"key":"B4","first-page":"104","article-title":"Advances in pharmacological treatment of migraine","volume":"22","author":"Li","year":"2022","journal-title":"Chin J Contemp Neurol Neurosurg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1016\/S0140-6736(20)32342-4","article-title":"Migraine: integrated approaches to clinical management and emerging treatments","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/j.1526-4610.2009.01424.x","article-title":"Acupuncture for treating acute attacks of migraine: a randomized controlled trial","volume":"49","author":"Li","year":"2009","journal-title":"Headache"},{"key":"B7","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/S1474-4422(06)70382-9","article-title":"Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial","volume":"5","author":"Diener","year":"2006","journal-title":"Lancet Neurol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"m697","DOI":"10.1136\/bmj.m697","article-title":"Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial","volume":"368","author":"Xu","year":"2020","journal-title":"Br Med J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1001\/jamainternmed.2016.9378","article-title":"The long-term effect of acupuncture for migraine prophylaxis: a randomized clinical trial","volume":"177","author":"Zhao","year":"2017","journal-title":"JAMA Intern Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4128","DOI":"10.1007\/s00415-020-10178-x","article-title":"Efficacy of acupuncture for migraine prophylaxis: a trial sequential meta-analysis","volume":"268","author":"Fan","year":"2021","journal-title":"J Neurol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1111\/j.1526-4637.2012.01376.x","article-title":"Efficacy of acupuncture for acute migraine attack: a multicenter single blinded, randomized controlled trial","volume":"13","author":"Wang","year":"","journal-title":"Pain Med"},{"key":"B12","first-page":"517","article-title":"Chinese guidelines for integrated traditional Chinese and Western medicine prevention and treatment of migraine (2022 version)","volume":"43","year":"2023","journal-title":"Chin J Integr Tradit West Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(97)10471-8","article-title":"Introducing a placebo needle into acupuncture research","volume":"352","author":"Streitberger","year":"1998","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1136\/aim.20.4.168","article-title":"Validating a new non-penetrating sham acupuncture device: two randomised controlled trials","volume":"20","author":"Park","year":"2002","journal-title":"Acupunct Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1472-6882-7-31","article-title":"A double-blind placebo needle for acupuncture research","volume":"7","author":"Takakura","year":"2007","journal-title":"BMC Complement Altern Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1001\/jama.2018.8907","article-title":"Effect of acupuncture vs sham acupuncture or waitlist control on joint pain related to aromatase inhibitors among women with early-stage breast cancer: a randomized clinical trial","volume":"320","author":"Hershman","year":"2018","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"777","DOI":"10.7326\/M19-2880","article-title":"Effect of acupuncture for postprandial distress syndrome: a randomized clinical trial","volume":"172","author":"Yang","year":"2020","journal-title":"Ann Intern Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.7326\/M21-1814","article-title":"Efficacy of acupuncture for chronic prostatitis\/chronic pelvic pain syndrome: a randomized trial","volume":"174","author":"Sun","year":"2021","journal-title":"Ann Intern Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s10194-024-01798-z","article-title":"Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021: insights from the global burden of disease study 2021","volume":"25","author":"Cen","year":"2024","journal-title":"J Headache Pain"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e058834","DOI":"10.1136\/bmjopen-2021-058834","article-title":"Characteristics and quality of clinical practice guidelines addressing acupuncture interventions: a systematic survey of 133 guidelines and 433 acupuncture recommendations","volume":"12","author":"Tang","year":"2022","journal-title":"BMJ Open"},{"key":"B21","doi-asserted-by":"publisher","first-page":"102991","DOI":"10.1016\/j.ctim.2023.102991","article-title":"Effectiveness and safety of scalp acupuncture for treating migraine: a systematic review and meta-analysis","volume":"78","author":"Kim","year":"2023","journal-title":"Complement Ther Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13643-025-02977-y","article-title":"Acupuncture improves migraine and quality of life in patients with migraine: a systematic review with meta-analysis","volume":"14","author":"Lu","year":"2025","journal-title":"Syst Rev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1136\/bmjebm-2022-112135","article-title":"Acupuncture for acute migraine attacks in adults: a systematic review and meta-analysis","volume":"28","author":"Wang","year":"2023","journal-title":"BMJ Evid Based Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/s11916-024-01312-9","article-title":"Anxiety disorders, anxious symptomology and related behaviors associated with migraine: a narrative review of prevalence and impact","volume":"29","author":"Raudensk\u00e1","year":"","journal-title":"Curr Pain Headache Rep"},{"key":"B25","doi-asserted-by":"publisher","year":"","DOI":"10.1371\/journal.pone.0324250"},{"key":"B26","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.cell.2016.05.069","article-title":"Integrated proteogenomic characterization of human high-grade serous ovarian cancer","volume":"166","author":"Zhang","year":"2016","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41593-021-00999-y","article-title":"Large-scale deep multi-layer analysis of Alzheimer\u2019s disease brain reveals strong proteomic disease-related changes not observed at the RNA level","volume":"25","author":"Johnson","year":"2022","journal-title":"Nat Neurosci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"6186","DOI":"10.1016\/j.cell.2025.08.038","article-title":"Multiscale proteomic modeling reveals protein networks driving Alzheimer\u2019s disease pathogenesis","volume":"188","author":"Wang","year":"2025","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"113165","DOI":"10.1016\/j.jpba.2020.113165","article-title":"Proteomic serum profile in menstrual-related and post menopause migraine","volume":"184","author":"Bellei","year":"2020","journal-title":"J Pharm Biomed Anal"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1939184\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:57:24Z","timestamp":1792666644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1939184\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":29,"alternative-id":["10.3389\/fmed.2026.1939184"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1939184","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"1939184"}}