{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:05:40Z","timestamp":1787616340865,"version":"build-2736575974"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"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. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Beta blockers are effective in migraine prevention. Low-dose combination therapy of blood pressure lowering is likely to lower blood pressure more than a beta-blocker, but there are no data on comparative efficacy of these treatments in migraine prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A double-blind, randomized, pilot trial in participants with episodic migraine to assess feasibility and tolerability of low-dose triple combination BP lowering (telmisartan 20\u202fmg, amlodipine 2.5\u202fmg and indapamide 1.25\u202fmg) vs. propranolol 160\u202fmg daily vs. matching placebos. The primary outcome was monthly headache days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between March 2017 and June 2018, 378 participants were screened and 30 were randomized (8%). The key reasons for ineligibility among screen failures were low blood pressure (86, 26%), unwilling to participate in a drug trial (76, 23%) and not meeting episodic migraine criteria (54, 16%). Among those randomized, mean age was 49\u202fyears, 83% female, baseline migraine frequency was 67\u202fh, aura present in 47%, mean baseline BP was 131\/87\u202fmmHg. As expected from a small pilot, the confidence intervals for treatment effect estimates were wide: reduction in monthly headache days for the low-dose triple were \u22120.6 (95% confidence interval [CI]\u202f\u22122.9, 1.8) and for propranolol \u22121.1 (95% CI \u22123.8, 1.6) compared to placebo. Tolerability was good, there were no dropouts from adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As a pilot study, the trial was not powered to detect efficacy; larger trials are required to determine the effect of low-dose triple combination blood pressure lowering on migraine. The medication was safe and well tolerated by participants with migraine; it is likely that study co-design with people with lived experience of migraine will benefit recruitment into the trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>ACTRN12616000937415, <jats:uri>https:\/\/anzctr.org.au\/<\/jats:uri>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1630732","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T04:12:21Z","timestamp":1757995941000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Blood pressure lowering for prevention of episodic migraine: results of a pilot randomized, placebo-controlled trial of combination blood pressure lowering medication with propranolol"],"prefix":"10.3389","volume":"16","author":[{"given":"Cheryl","family":"Carcel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faraidoon","family":"Haghdoost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Cordato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Balicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Freed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig 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