Cabergoline as a Preventive Migraine Treatment: An Investigator-Initiated Randomized Controlled Trial

Background Beneficial effects of dopamine agonist treatment on migraine have been reported but remain to be properly tested. Aim to examine the effect of cabergoline as preventive treatment for migraine. Primary endpoint Change in monthly migraine days (MMD). Methods In a randomized, double-blind, placebo-controlled pilot study, 36 adults with episodic and chronic migraine were enrolled. Following a 28-days baseline period, participants received cabergoline 0.5 mg or placebo once weekly for 12 weeks as add-on treatment. An electronic headache diary was completed by the participant, and pertinent headache questionnaires and blood tests were collected at baseline and following the treatment period. The trial was registered with [ClinicalTrials.gov][1] ([NCT05525611][2]). Findings Mean (SD) baseline MMD was 13.6 (4.1) in the cabergoline group and 14.0 (5.3) in the placebo group. In participants with episodic migraine (n= 20), the change in mean MMD (SE) from baseline to the last 28 days of the treatment period was -5.4 (1.3) (cabergoline) as compared to -1.8 (0.9) (placebo) [odds ratio: 0.79 (95% CI 0.65 - 0.95), p=0.014]. In participants with chronic migraine (n=13), the reduction in MMD with cabergoline was not significant (p=0.6). Patients’ global impression of change significantly improved after cabergoline as compared to placebo in the entire group of participants (p=0.006). The number of participants with episodic migraine achieving ≥ 50% reduction in MMD tended to increase after cabergoline (p=0.07). Seven participants receiving cabergoline and 4 participants receiving placebo experienced adverse effects, none of which were serious. Interpretations Preventive cabergoline treatment exhibited clinically meaningful improvement in episodic migraine without serious adverse effects. This provides proof-of-concept to justify a sufficiently powered phase 2 trial with different cabergoline dosing regimens as preventive treatment of episodic migraine. Funding This study has received no external funding. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05525611 ### Funding Statement This study did not receive any external funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee for the Central Denmark Region gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: https://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05525611&atom=%2Fmedrxiv%2Fearly%2F2023%2F12%2F29%2F2023.12.27.23300273.atom