{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:04:23Z","timestamp":1792515863740,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012175","name":"Zhejiang Provincial Administration of Traditional Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012175","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Functional dyspepsia (FD) is a prevalent health issue currently lacking optimal treatment options, with its global incidence rate increasing in recent years. Clinical studies have recently focused on the application of auriculotherapy in functional gastrointestinal disorders that are accompanied by negative emotions. However, few randomized controlled trials have investigated the use of auriculotherapy for FD patients with insomnia, leaving the therapeutic efficacy and safety largely undefined. This study aims to evaluate the clinical efficacy and safety of auriculotherapy in treating FD patients with insomnia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>This study is a single-center, randomized controlled clinical trial involving 80 patients with FD and insomnia. Using a central randomization system, the subjects are randomly assigned to the auricular acupressure group or the sham auricular acupressure group at a 1:1 ratio, with the auricular acupressure group targeting the concha region and the sham auricular acupressure group targeting the earlobe region. The primary outcome is the response rate at 2\u202fweeks, and the secondary outcomes include the response rate at 8\u202fweeks, sleep data assessed by actigraphy, modified Functional Dyspepsia Symptom Diary, short form-Nepean Dyspepsia Index, Self-rated Anxiety Scale, Self-rated Depression Scale, High Arousal Scale, and Heart Rate Variability. Efficacy results will be evaluated at baseline and at 2 and 8\u202fweeks after treatment. Adverse events will be monitored throughout the study observation period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results of this trial are anticipated to validate the efficacy and safety of auriculotherapy in improving symptoms of FD and insomnia, as well as in reducing negative emotional states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>, NCT06466044. Registered 14th May 2024, <jats:ext-link>https:\/\/register.clinicaltrials.gov<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1496502","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:03:06Z","timestamp":1741766586000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The efficacy and safety of auricular acupoint therapy on treating functional dyspepsia with insomnia: study protocol for a randomized controlled trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Meng-Yuan","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Yi","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Jiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Dan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Dong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Nong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1097\/MOG.0000000000000306","article-title":"Functional dyspepsia","volume":"32","author":"Talley","year":"2016","journal-title":"Curr Opin Gastroenterol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1136\/gutjnl-2022-327737","article-title":"British Society of Gastroenterology guidelines on the management of functional dyspepsia","volume":"71","author":"Black","year":"2022","journal-title":"Gut"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/S2468-1253(18)30003-7","article-title":"Epidemiology, clinical characteristics, and associations for symptom-based RomeIV functional dyspepsia in adults in the USA, Canada, and the UK: across-sectional population-based study","volume":"3","author":"Aziz","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1056\/NEJMra1501505","article-title":"Functional dyspepsia","volume":"373","author":"Talley","year":"2015","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"17081","DOI":"10.1038\/nrdp.2017.81","article-title":"Functional dyspepsia","volume":"3","author":"Enck","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/nmo.12657","article-title":"Clinical and epidemiological differences in functional dyspepsia between the east and the west","volume":"28","author":"Mahadeva","year":"2016","journal-title":"Neurogastroenterol Motil"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"814","DOI":"10.3390\/ijms25020814","article-title":"Molecular mechanisms of Reelin in the enteric nervous system and the microbiota-gut-brain Axis: implications for depression and antidepressant therapy","volume":"25","author":"Halvorson","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3748\/wjg.v26.i5.456","article-title":"Diet and functional dyspepsia: clinical correlates and therapeutic perspectives","volume":"26","author":"Pesce","year":"2020","journal-title":"World J Gastroenterol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00384-023-04333-9","article-title":"The role of psychological factors in functional gastrointestinal disorders: a systematic review and meta-analysis","volume":"38","author":"Yan","year":"2023","journal-title":"Int J Color Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.cgh.2011.02.010","article-title":"Functional dyspepsia is associated with sleep disorders","volume":"9","author":"Lacy","year":"2011","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1272\/jnms.80.104","article-title":"Sleep disorders in functional dyspepsia and future therapy","volume":"80","author":"Futagami","year":"2013","journal-title":"J Nippon Med Sch"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1159\/000532082","article-title":"Functional dyspepsia: current understanding and future perspective","volume":"105","author":"Oshima","year":"2024","journal-title":"Digestion"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1007\/s10620-021-07017-y","article-title":"Frequency, intensity, and partner of exercise habit is inversely associated with functional dyspepsia in young Japanese population","volume":"67","author":"Furukawa","year":"2022","journal-title":"Dig Dis Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"682783","DOI":"10.3389\/fmed.2021.682783","article-title":"Acupuncture as an add-on treatment for functional dyspepsia: a systematic review and Meta-analysis","volume":"8","author":"Kwon","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/S1047-9651(18)30180-3","article-title":"Auricular acupuncture and auricular medicine","volume":"10","author":"Soliman","year":"1999","journal-title":"Phys Med Rehabil Clin N Am"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12877-023-03881-7","article-title":"Effectiveness of auricular acupressure on constipation and related quality of life among the older people in the residential care home: a randomized clinical trial","volume":"23","author":"Aminizadeh","year":"2023","journal-title":"BMC Geriatr"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"5028","DOI":"10.1038\/srep05028","article-title":"Auricular acupressure reduces anxiety levels and improves outcomes of in vitro fertilization: a prospective, randomized and controlled study","volume":"4","author":"Qu","year":"2014","journal-title":"Sci Rep"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"58984","DOI":"10.3791\/58984","article-title":"Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): technique, targeting, and considerations","volume":"143","author":"Badran","year":"2019","journal-title":"J Vis Exp"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.jad.2016.02.031","article-title":"Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study","volume":"195","author":"Rong","year":"2016","journal-title":"J Affect Disord"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e7586","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1053\/j.gastro.2016.02.032","article-title":"Functional gastrointestinal disorders: history, pathophysiology","volume":"150","author":"Drossman","year":"2016","journal-title":"Clin Features Rome IV Gastroenterol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3760\/cma.j.cn113694-20240406-00209","article-title":"Chinese guideline for diagnosis and treatment of insomnia (2023)","volume":"57","year":"2023","journal-title":"Chin J Neurol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1386108","DOI":"10.3389\/fnins.2024.1386108","article-title":"Objectivization study of acupuncture Deqi and brain modulation mechanisms: a review","volume":"18","author":"Zhong","year":"2024","journal-title":"Front Neurosci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.3390\/brainsci12101296","article-title":"Transcutaneous Vagus nerve stimulation could improve the effective rate on the quality of sleep in the treatment of primary insomnia: a randomized control trial","volume":"12","author":"Wu","year":"2022","journal-title":"Brain Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/S2213-8587(20)30107-8","article-title":"A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial","volume":"8","author":"Ferrara","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"521","DOI":"10.14309\/ajg.0000000000002548","article-title":"Transcutaneous auricular vagal nerve stimulation is effective for the treatment of functional dyspepsia: a multicenter, randomized controlled study","volume":"119","author":"Shi","year":"2024","journal-title":"Am J Gastroenterol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1097\/MEG.0000000000001314","article-title":"The Nepean dyspepsia index is a valid instrument for measuring quality-of-life in functional dyspepsia","volume":"31","author":"Jones","year":"2019","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0033-3182(71)71479-0","article-title":"A rating instrument for anxiety disorders","volume":"12","author":"Zung","year":"1971","journal-title":"Psychosomatics"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1186\/s12888-017-1489-6","article-title":"Screening for anxiety and depression: reassessing the utility of the Zung scales","volume":"17","author":"Dunstan","year":"2017","journal-title":"BMC Psychiatry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1176\/ajp.150.10.1529","article-title":"Daytime alertness in patients with primary insomnia","volume":"150","author":"Regestein","year":"1993","journal-title":"Am J Psychiatry"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"116072","DOI":"10.1016\/j.neuroimage.2019.116072","article-title":"Heart rate variability as a biomarker in health and affective disorders: a perspective on neuroimaging studies","volume":"202","author":"Mulcahy","year":"2019","journal-title":"NeuroImage"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"5416","DOI":"10.1002\/hbm.26449","article-title":"Clinical-functional brain connectivity signature predicts longitudinal symptom improvement after acupuncture treatment in patients with functional dyspepsia","volume":"44","author":"Yin","year":"2023","journal-title":"Hum Brain Mapp"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"154160","DOI":"10.1016\/j.phymed.2022.154160","article-title":"Acupuncture for cancer-related insomnia: a systematic review and meta-analysis","volume":"102","author":"Zhang","year":"2022","journal-title":"Phytomedicine"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1146\/annurev-med-042320-014032","article-title":"The gut-brain Axis","volume":"73","author":"Mayer","year":"2022","journal-title":"Annu Rev Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1126\/science.abi6087","article-title":"Signaling inflammation across the gut-brain axis","volume":"374","author":"Agirman","year":"2021","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.brs.2019.12.018","article-title":"Non-invasive stimulation of vagal afferents reduces gastric frequency","volume":"13","author":"Teckentrup","year":"2020","journal-title":"Brain Stimul"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","article-title":"Proton pump inhibitors affect the gut microbiome","volume":"65","author":"Imhann","year":"2016","journal-title":"Gut"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1176\/appi.ajp.20230356","article-title":"Real-world evidence on clinical outcomes of commonly used antidepressants in older adults initiating antidepressants for depression: a Nationwide cohort study in Denmark","volume":"181","author":"Ishtiak-Ahmed","year":"2024","journal-title":"Am J Psychiatry"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1037\/ccp0000881","article-title":"Acceptance and commitment therapy versus cognitive behavioral therapy for insomnia: a randomized controlled trial","volume":"92","author":"El Rafihi-Ferreira","year":"2024","journal-title":"J Consult Clin Psychol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2024\/8872685","article-title":"Effectiveness of mindfulness-based stress reduction on mental health and psychological quality of life among university students: a GRADE-assessed systematic review","volume":"2024","author":"Pan","year":"2024","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e0298438","DOI":"10.1371\/journal.pone.0298438","article-title":"Efficacy of acupuncture for anxiety and depression in functional dyspepsia: a systematic review and meta-analysis","volume":"19","author":"Xu","year":"2024","journal-title":"PLoS One"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"155481","DOI":"10.1016\/j.phymed.2024.155481","article-title":"Insights and future prospects of traditional Chinese medicine in the treatment of functional dyspepsia","volume":"127","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/8868720","article-title":"Efficacy of auricular acupressure in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with Cancer: a systematic review and Meta-analysis","volume":"2021","author":"Chen","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"E24","DOI":"10.1097\/SGA.0000000000000332","article-title":"Effects of auricular acupressure on women with irritable bowel syndrome","volume":"43","author":"Go","year":"2020","journal-title":"Gastroenterol Nurs"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.brs.2022.09.003","article-title":"The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: a double blinded randomized clinical trial","volume":"15","author":"Wang","year":"2022","journal-title":"Brain Stimul"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13058-023-01645-0","article-title":"Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial","volume":"25","author":"Zhang","year":"2023","journal-title":"Breast Cancer Res"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1496502\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:03:10Z","timestamp":1741766590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1496502\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":47,"alternative-id":["10.3389\/fmed.2025.1496502"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1496502","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]},"article-number":"1496502"}}