Cabergoline for Episodic Migraine

NCT ID: NCT07072910

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-12
• Study Completion Date: 2028-09-01

Brief 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.

Detailed Description

Migraine is a common and often disabling neurological disorder. While there are several treatments available, many individuals continue to experience frequent attacks, side effects from medications, or limited access to newer therapies due to high costs.

Cabergoline is a medication that activates dopamine receptors and has shown promising effects in migraine. A small, pilot study found that a low dose of cabergoline (0.5 mg per week) reduced the number of migraine days per month in patients with episodic migraine. It was well tolerated, with few side effects and good treatment adherence.

The PROTECT trial is a larger clinical study that aims to confirm these results. The trial will evaluate whether cabergoline, taken once weekly, is effective in reducing the number of monthly migraine days compared to placebo. It will also test a higher dose (1.0 mg/week) to investigate whether a stronger effect can be achieved without increasing side effects.

The trial consists of two treatment phases. In the first phase, participants will be randomly assigned to receive either cabergoline 0.5 mg, cabergoline 1.0 mg, or placebo once weekly for 12 weeks. In the second phase, all participants will receive cabergoline for another 12 weeks, in an open-label setting. This will allow researchers to study longer-term treatment effects, adherence, and tolerability. A final safety follow-up phase will last four weeks.

Throughout the study, participants will report their migraine symptoms, medication use, and headache severity in a secure electronic diary. They will also complete questionnaires about headache-related disability, work productivity, and overall improvement. Blood samples will be collected to study the underlying biological mechanisms of migraine, and explore whether certain genetic or hormonal markers can help predict who benefits most from cabergoline.

The main outcome of the study is the change in the number of monthly migraine days during the last four weeks of the double-blind phase. Other outcomes include changes in headache severity, use of acute medication, and quality-of-life scores. The study will also monitor changes in health markers such as cholesterol, inflammation, and prolactin levels.

The PROTECT trial will include adults with episodic migraine (defined as having 4 to 14 migraine days per month). Participants must be at least 18 years old and have had a stable pattern of migraine attacks and acute treatment for the past three months. People with chronic migraine, certain headache types, or other medical conditions will not be eligible.

Participants will be recruited from headache clinics, general practitioners, and online platforms. All participants will provide written informed consent before entering the study.

This trial is conducted by an independent academic research group and is designed to evaluate a low-cost, well-known medication for a new use. If successful, cabergoline could provide a new, accessible preventive option for people with migraine.

Conditions

Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cabergoline 0.5 mg/Week (Double-Blind Phase)

Participants in this arm will receive cabergoline 0.5 mg once weekly as add-on treatment for 12 weeks during the double-blind treatment phase.

Group Type: EXPERIMENTAL

Cabergoline 0.5 MG

Intervention Type: DRUG

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.

Cabergoline 1.0 mg/Week (Double-Blind Phase)

Participants in this arm will receive cabergoline 1.0 mg once weekly as add-on treatment for 12 weeks during the double-blind treatment phase.

Group Type: EXPERIMENTAL

Cabergoline 1 MG

Intervention Type: DRUG

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.

Placebo (Double-Blind Phase)

Participants in this arm will receive a placebo once weekly as add-on treatment for 12 weeks during the double-blind treatment phase.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Cabergoline 0.5 MG

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Cabergoline 1 MG

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.

Intervention Type: DRUG

Other Intervention Names

Dopamine receptor agonist; Dostinex; Dopamine receptor agonist; Dostinex

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Episodic migraine according to ICHD-3 criteria
• 4-14 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 Criteria

• < 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Aarhus University Hospital

Aarhus N, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Astrid Hjelholt, M.D., Ph.D.

Role: CONTACT

ajh@clin.au.dk

004524800664

Facility Contacts

Astrid Hjelholt, MD, PhD

Role: primary

auh.team.protect@rm.dk

+4551730476

References

Hjelholt AJ, Bach FW, Kasch H, Stovring H, Jensen TS, Jorgensen JOL. Cabergoline as a preventive migraine treatment: A randomized clinical pilot trial. PLoS One. 2025 Apr 1;20(4):e0320937. doi: 10.1371/journal.pone.0320937. eCollection 2025.

Reference Type: BACKGROUND

PMID: 40168298 (View on PubMed)

Other Identifiers

2025-522323-10-00

Identifier Type: CTIS

Identifier Source: secondary_id

AU-PROTECT-2025

Identifier Type: -

Identifier Source: org_study_id