Cabergoline for Episodic Migraine
Prevention and Treatment of Episodic Migraine by Cabergoline Therapy (PROTECT). A Randomized, Placebo-controlled, Double-blind, Investigator-initiated Trial
Aarhus University Hospital
150 participants
Nov 12, 2025
INTERVENTIONAL
Conditions
Summary
The goal of this randomized, placebo-controlled, double-blind clinical trial is to evaluate the efficacy, safety, and tolerability of cabergoline for the prevention of episodic migraine in adults with 4-14 monthly migraine days (MMD). The main questions it aims to answer are: 1. Does once-weekly cabergoline (0.5 mg or 1.0 mg) reduce MMD compared to placebo? 2. What are the effects of cabergoline on headache severity, acute medication use, and patient-reported outcomes? 3. Is cabergoline safe to use in individuals with migraine? Participants will: Complete a 4-week baseline period to document migraine frequency and classify headache days. Be randomly assigned to one of three treatment arms: 1. Cabergoline 0.5 mg/week 2. Cabergoline 1.0 mg/week 3. Placebo Participate in a 12-week double-blind treatment phase, followed by a 12-week open-label treatment phase where all participants receive cabergoline (0.5 mg or 1.0 mg once weekly). Record daily headache activity, acute medication use, and severity using an electronic diary. Complete validated headache questionnaires and provide blood samples for biomarker analysis at baseline, week 12, and week 24. The study also includes exploratory analyses of genetic predictors of treatment response and metabolic markers to assess the broader effects of cabergoline.
Eligibility
Inclusion Criteria5
- Age ≥18 years
- Episodic migraine according to ICHD-3 criteria
- -14 monthly migraine days (MMD) in the last 3 months prior to inclusion
- Stable acute migraine medication use for at least 3 months prior to inclusion
- Written informed consent
Exclusion Criteria17
- < 4 MMD or ≥ 15 MMD during the baseline period
- Chronic migraine (≥15 headache days per month)
- Trigeminal autonomic cephalalgias and neuralgias
- Secondary headache conditions
- Other common primary headache types (e.g. tension-type headache) if attacks are frequent (present on an average of >1 day/month and >12 days/year)
- Presumed medication-overuse headache
- Recent changes in preventive migraine treatment (≥3 months prior to study inclusion)
- History of pulmonary, retroperitoneal, or pericardial disorders, including heart valve disease
- Severe untreated hypertension
- Use of drugs with dopamine antagonistic or agonistic properties
- Psychiatric disorders requiring pharmacological treatment
- Women of child-bearing potential (i.e. not chemically or surgically sterilized, or not postmeno-pausal) and male participants with partners of child-bearing potential, who are unwilling to use a medically accepted method of contraception, considered reliable by the investigator, from signing of informed consent and throughout the study
- Women who have a positive pregnancy test at randomization
- Women who are breast-feeding
- Allergy or hypersensitivity to cabergoline or similar compounds
- Concurrent participation in another clinical trial that, in the judgement of the investigator, may interfere with the conduct or outcomes of the present study
- Inability of the subject, in the opinion of the investigator, to understand and/or comply with study medications or procedures, or any conditions that, in the opinion of the investigator, may render the subject unable to complete the study
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Interventions
Participants will receive cabergoline 0.5 mg as oral tablets, taken once weekly as an add-on treatment for 12 weeks during the double-blind treatment phase. Participants who received cabergoline 0.5 mg during the double-blind phase will continue with the same 0.5 mg dose in the open-label phase.
Participants will receive placebo as oral tablets, taken once weekly as an add-on treatment for 12 weeks during the double-blind treatment phase. In the open-label phase, these participants will transition to active cabergoline treatment, receiving either 0.5 mg or 1.0 mg once weekly, depending on their randomized allocation at the start of the open-label phase. The placebo tablets will be formulated to match the cabergoline tablets in size, shape, and color, and should be taken under the same conditions.
Participants will receive cabergoline 1.0 mg as oral tablets, taken once weekly as an add-on treatment for 12 weeks during the double-blind treatment phase. Participants who received cabergoline 1.0 mg during the double-blind phase will continue with the same 1.0 mg dose in the open-label phase.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07072910