{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:43:08Z","timestamp":1772980988041,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["1146\u201000023B"],"award-info":[{"award-number":["1146\u201000023B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018703","name":"HORIZON EUROPE European Innovation Council","doi-asserted-by":"publisher","award":["190133087"],"award-info":[{"award-number":["190133087"]}],"id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2026,2]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n Evaluate the efficacy and safety of a novel partial rebreathing device for early treatment of acute attacks of migraine with aura.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Earlier clinical studies have indicated a potential for CO\n 2<\/jats:sub>\n \u2013enriched gas to be effective for acute treatment of migraine with aura, especially when applied during the early part of the aura stage. We developed a partial rebreathing device inducing moderate, steady\u2010state hypercapnia with normoxia in order to provide a carbon dioxide delivery system combining efficacy, usability, safety, and affordability.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This randomized, double\u2010blind, sham\u2010controlled, parallel\u2010group, group\u2010sequential study was conducted at 15 study sites, nine located in the United States and six in Germany, between March 2023 and February 2025. The study enrolled patients aged 18\u201365\u2009years with migraine with aura. The study had a sequential two\u2010stage study design. At the beginning of stage 1, participants were randomized to active or sham and treated up to four attacks. Participants were instructed to treat from the onset of aura and until 5 min after aura cessation. After having reported four attacks in stage 1, participants had the option to continue into stage 2, an open\u2010label extension in which they could treat up to five attacks with the active device. During stage 1, participants recorded symptom scores in a study diary app at the onset of aura and after 1, 2, 24, and 48\u2009h.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The study was terminated at the interim analysis point due to the lack of effect, at which point 142 participants had been enrolled (mean age 39.2\u2009years, 81% women [115\/142]). Sixty\u2010seven participants had reported at least one study attack by the time of the study termination.<\/jats:p>\n \n None of the primary or secondary endpoints reached statistical significance. The primary endpoint\n Absence of Moderate or Severe Pain at 2\u2009hours<\/jats:italic>\n was 69.7% (46\/66) [95.2% confidence interval (CI), 48.5, 90.9] in the sham group and 60.0% (42\/70) [95.2% CI, 37.6, 82.4] in the active group (\n p<\/jats:italic>\n \u2009=\u20090.379), whereas\n Pain Freedom at 2\u2009hours<\/jats:italic>\n was 18.2% (12\/66) [95.2% CI, 1.3, 35.1] in the sham group and 21.4% (15\/70) [95.2% CI, 3.6, 39.2] in the active group (\n p<\/jats:italic>\n \u2009=\u20090.717).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Partial rebreathing inducing moderate hypercapnia with normoxia was not effective for aura\u2010stage treatment of migraine\u2010with\u2010aura attacks.<\/jats:p>\n \n The study was preregistered at\n ClinicalTrials.gov<\/jats:ext-link>\n (registration number NCT05546385).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/head.15090","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T04:24:17Z","timestamp":1763785457000},"page":"417-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Partial rebreathing is not effective for early treatment of migraine with aura attacks: Results of a double\u2010blind, randomized, controlled trial (\n PAREMA1<\/scp>\n )"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9362-3711","authenticated-orcid":false,"given":"Charly","family":"Gaul","sequence":"first","affiliation":[{"name":"Headache Center Frankfurt Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f3nia","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Rehaler Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troels","family":"Johansen","sequence":"additional","affiliation":[{"name":"Rehaler Copenhagen Denmark"},{"name":"Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01718-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183717"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1950.02310190048002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.284.6312.312"},{"key":"e_1_2_11_6_1","unstructured":"SpieringsE.Non\u2010inhaled intranasal carbon dioxide for the abortive treatment of migraine headache: efficacy tolerability and safety. 130th Annual Meeting of the American Neurological Association (ANA) San Diego CA.2005: 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