MigrainePhase 2PROTECTNCT07072910
Cabergoline for Episodic Migraine
A Phase 2 study testing Cabergoline 0.5 MG and Cabergoline 1 MG in people with Migraine, run by Aarhus University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Migraine
- What is being tested?
- Cabergoline 0.5 MG and Cabergoline 1 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteDenmark
- Study dates
- 12 Nov 2025to 1 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- < 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Aarhus University Hospital
Aarhus N, 8200
Astrid Hjelholt, MD, PhD, +4551730476, auh.team.protect@rm.dk
About this study
Official title: Prevention and Treatment of Episodic Migraine by Cabergoline Therapy (PROTECT). A Randomized, Placebo-controlled, Double-blind, Investigator-initiated Trial
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:
- Does once-weekly cabergoline (0.5 mg or 1.0 mg) reduce MMD compared to placebo?
- What are the effects of cabergoline on headache severity, acute medication use, and patient-reported outcomes?
- Is cabergoline safe to use in individuals with migraine?
Read more
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:
- Cabergoline 0.5 mg/week
- Cabergoline 1.0 mg/week
- 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.
Read the 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
- Being tested
- Cabergoline 0.5 MG, Placebo, Cabergoline 1 MG
- Keywords
- Migraine, Preventive treatment, Cabergoline, Drug repurposing
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabergoline 0.5 MGDrug
Also called Dopamine receptor agonist, Dostinex
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.
PlaceboDrug
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.
Cabergoline 1 MGDrug
Also called Dopamine receptor agonist, Dostinex
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.
| Study group | Role | What they receive |
|---|---|---|
| Cabergoline 0.5 mg/Week (Double-Blind Phase) | Experimental | 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. Receives: Drug: Cabergoline 0.5 MG |
| Cabergoline 1.0 mg/Week (Double-Blind Phase) | Experimental | 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. Receives: Drug: Cabergoline 1 MG |
| Placebo (Double-Blind Phase) | Placebo comparator | Participants in this arm will receive a placebo once weekly as add-on treatment for 12 weeks during the double-blind treatment phase. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Monthly Migraine Days (MMD)
Change in MMD from baseline to the last four weeks of the double-blind treatment phase.
Migraine days are defined according to ICHD-3 criteria or the use of migraine-specific acute medication, recorded in a daily, electronic diary.
Measured: Baseline to the last four weeks of the double-blind treatment phase
Secondary outcomes (33)
Responder rate (proportion of participants achieving ≥50% reduction in MMD)
Proportion of participants achieving ≥50% reduction in MMD during the last four weeks of the 12-week double-blind treatment phase (50% responder rate).
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Change in number of moderate/severe headache days
Change in number of moderate/severe headache days from baseline to the last four weeks of the double-blind treatment phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Headache severity
Proportion of attacks classified as mild, moderate, or severe at the last four weeks of the double-blind treatment phase.
Measured: The last four weeks of the double-blind treatment phase.
Changes in acute medication use.
Change in number of days with use of acute migraine-specific medication from baseline to the last four weeks of the double-blind treatment phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Migraine Disability Assessment Scale (MIDAS)
Change in MIDAS score from baseline to the end of the double-blind treatment phase. MIDAS assesses migraine-related disability over a 3-month recall period. It contains five questions regarding number of days of missed work/school, reduced productivity at work/school, missed household work, reduced productivity in household work, and missed family and/or social activities. A higher score indicates greater disability.
Measured: Baseline to the end of the double-blind treatment phase (week 12).
Headache Impact Test - 6 items (HIT-6)
Change in HIT-6 score from baseline to the end of the double-blind treatment phase. HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. A higher score indicates greater disability.
Measured: Baseline to the end of the double-blind treatment phase (week 12).
Work Productivity and Activity Impairment (WPAI)
Change in WPAI score from baseline to the end of the double-blind treatment phase. WPAI Questionnaire is a 6-item instrument to measure impairments over the past 7 days in both paid work and unpaid work due to one's health. A higher score indicates greater disability.
Measured: Baseline to the end of the double-blind treatment phase (week 12).
Patient's Global Impression of Change (PGIC)
PGIC score at the end of the double-blind treatment phase.
Measured: The end of the double-blind treatment phase (Week 12)
Safety and tolerability of cabergoline (incidence of adverse events)
Incidence of adverse events during the trial.
Measured: From the beginning of the treatment phase (week 0) until the end of the safety follow-up (week 28).
Sustained effect of cabergoline treatment in change in MMD.
Change in MMD assessed from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effect of cabergoline on responder rate (defined as the proportion of participants achieving a ≥50% reduction in monthly migraine days).
Proportion of participants achieving ≥50% reduction in MMD assessed from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline on the frequency of moderate/severe headache days.
Number of moderate/severe headache days assessed from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on acute medication use.
Acute medication use assessed from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on HIT-6 score.
Change in HIT-6 score from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on MIDAS score.
Change in MIDAS score from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on WPAI score.
Change in WPAI score from baseline and from the end of the double-blind phase to the end of the open-label phase.
Measured: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on PGIC.
PGIC (participant's overall perception of change since starting study medication) assessed at the end of the double-blind phase compared to the end of the open-label phase.
Measured: The end of the double-blind phase (week 12) and the end of the open-label phase (week 24).
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on MMD
Change in MMD from baseline to the last four weeks of the double-blind phase in any treatment (0.5 mg or 1.0 mg) versus placebo.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on responder rate
Proportion of participants achieving ≥50% reduction in MMD in the group receiving cabergoline (0.5 mg or 1.0 mg) compared to placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on number of moderate/severe headache days
Number of moderate/severe headache days with any treatment (0.5 mg or 1.0 mg) versus placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on acute medication use
Acute medication use with any treatment (0.5 mg or 1.0 mg) versus placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on HIT-6
HIT-6 score with any treatment (0.5 mg or 1.0 mg) versus placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on MIDAS
MIDAS score with any treatment (0.5 mg or 1.0 mg) versus placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on WPAI
WPAI with any treatment (0.5 mg or 1.0 mg) versus placebo from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on PGIC
PGIC (participant's overall perception of change since starting study medication) with any treatment (0.5 mg or 1.0 mg) versus placebo after the double-blind treatment phase.
Measured: The end of the double-blind treatment phase (week 12).
Dose-Response Analysis of Change in Monthly Migraine Days (MMD)
Monthly Migraine Days (MMD) will be assessed as the change from baseline to the last four weeks of the double-blind phase. MMD is defined as the number of migraine days per 28-day period, recorded via electronic headache diary. The dose-response relationship will be evaluated by comparing the change in MMD across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of ≥50% Responder Rate in Monthly Migraine Days.
Responder rate is defined as the proportion of participants achieving a ≥50% reduction in Monthly Migraine Days (MMD) from baseline to the last four weeks of the double-blind phase. MMD is measured as the number of migraine days per 28-day period, recorded via electronic headache diary. The dose-response relationship will be assessed by comparing responder rates across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Moderate/Severe Headache Days
Moderate/severe headache days will be assessed as the number of days per 28-day period with a headache rated as moderate or severe in intensity, based on daily entries in an electronic headache diary. A dose-response relationship will be evaluated by comparing moderate/severe headache days across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model. The outcome is defined as the change from baseline to the last four weeks of the double-blind phase.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Acute Migraine Medication Use
Acute medication use is defined as the number of days per 28-day period on which any acute migraine-specific medication (e.g., triptans or gepants) is used, based on entries in an electronic headache diary. The outcome is assessed as the change from baseline to the last four weeks of the double-blind phase. A dose-response relationship will be evaluated by comparing acute medication use across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of HIT-6 Total Score
The Headache Impact Test-6 (HIT-6) assesses the impact of headache on daily functioning, including pain, social functioning, and cognitive performance. The total score ranges from 36 to 78, with higher scores indicating greater headache-related disability. The outcome is defined as the change in HIT-6 total score from baseline to the last four weeks of the double-blind phase. A dose-response relationship will be evaluated by comparing HIT-6 score changes across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of MIDAS Total Score
The Migraine Disability Assessment (MIDAS) questionnaire evaluates headache-related disability over a 3-month period. Higher scores indicate greater disability. The outcome is defined as the change in MIDAS total score from baseline to the last four weeks of the double-blind phase. A dose-response relationship will be evaluated by comparing changes in MIDAS score across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Total WPAI (Migraine) Score
The Work Productivity and Activity Impairment Questionnaire - Migraine version (WPAI:Migraine V2.0) is a validated instrument assessing the impact of migraine on work productivity and daily activities over the past seven days. The total score combines absenteeism, presenteeism, and activity impairment into a composite percentage ranging from 0% (no impairment) to 100% (complete impairment). The outcome is defined as the change in total WPAI score from baseline to the last four weeks of the double-blind phase. A dose-response relationship will be evaluated by comparing total scores across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Patient Global Impression of Change (PGIC)
The Patient Global Impression of Change (PGIC) is a single-item patient-reported outcome measuring the participant's overall perception of change in their condition since the start of study treatment. The outcome is defined as the PGIC score at the end of the double-blind phase. A dose-response relationship will be evaluated by comparing PGIC scores across the three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
Measured: Baseline to the last four weeks of the double-blind treatment phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start12 Nov 2025
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The PROTECT trial is a randomized, double-blind, placebo-controlled study. It includes: 1. A baseline phase (Weeks -4-0): Participants complete a daily headache diary to document migraine frequency and classify headache days. 2. A Double-Blind Phase (Weeks 0-12): Participants receive cabergoline 0.5 mg/week, cabergoline 1.0 mg/week, or placebo. 3. An Open-Label Phase (Weeks 12-24): All participants receive cabergoline (0.5 mg or 1.0 mg) once weekly. 4. A Safety Follow-Up Phase (Weeks 24-28): Participants are monitored for adverse events after discontinuation.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07072910
- Sponsor's protocol ID
- AU-PROTECT-2025
- Other IDs
- 2025-522323-10-00, 2025
- Acronym
- PROTECT
- Status last verified
- Nov 2025
- First submitted
- 19 May 2025
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) will be shared with researchers upon reasonable request, including baseline characteristics, outcome measures, and adverse events. Data will be available upon publication of the primary manuscript and for a minimum of 5 years. Requests should be directed to the Principal Investigator at ajh@clin.au.dk. Access will be granted upon approval of a data sharing agreement
Publications
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.
PubMed 40168298
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention and Treatment of Episodic Migraine by Cabergoline Therapy (PROTECT). A Randomized, Placebo-controlled, Double-blind, Investigator-initiated Trial
- ClinicalTrials.gov ID
- NCT07072910
- Acronym / sponsor ID
- PROTECT / AU-PROTECT-2025
- Conditions
- Migraine
- Keywords
- Migraine, Preventive treatment, Cabergoline, Drug repurposing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- 12 Nov 2025 (actual)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 18 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does once-weekly cabergoline (0.5 mg or 1.0 mg) reduce MMD compared to placebo?
- What are the effects of cabergoline on headache severity, acute medication use, and patient-reported outcomes?
- 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:
- Cabergoline 0.5 mg/week
- Cabergoline 1.0 mg/week
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- The PROTECT trial is a randomized, double-blind, placebo-controlled study. It includes: 1. A baseline phase (Weeks -4-0): Participants complete a daily headache diary to document migraine frequency and classify headache days. 2. A Double-Blind Phase (Weeks 0-12): Participants receive cabergoline 0.5 mg/week, cabergoline 1.0 mg/week, or placebo. 3. An Open-Label Phase (Weeks 12-24): All participants receive cabergoline (0.5 mg or 1.0 mg) once weekly. 4. A Safety Follow-Up Phase (Weeks 24-28): Participants are monitored for adverse events after discontinuation.
| Arm | Type | Receives |
|---|---|---|
| Cabergoline 0.5 mg/Week (Double-Blind Phase) | Experimental | Drug: Cabergoline 0.5 MGParticipants in this arm will receive cabergoline 0.5 mg once weekly as add-on treatment for 12 weeks during the double-blind treatment phase. |
| Cabergoline 1.0 mg/Week (Double-Blind Phase) | Experimental | Drug: Cabergoline 1 MGParticipants in this arm will receive cabergoline 1.0 mg once weekly as add-on treatment for 12 weeks during the double-blind treatment phase. |
| Placebo (Double-Blind Phase) | Placebo comparator | Drug: PlaceboParticipants in this arm will receive a placebo once weekly as add-on treatment for 12 weeks during the double-blind treatment phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- < 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cabergoline 0.5 MGAlso: Dopamine receptor agonist, DostinexParticipants 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. | Drug | Cabergoline 0.5 mg/Week (Double-Blind Phase) |
| PlaceboParticipants 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. | Drug | Placebo (Double-Blind Phase) |
| Cabergoline 1 MGAlso: Dopamine receptor agonist, DostinexParticipants 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. | Drug | Cabergoline 1.0 mg/Week (Double-Blind Phase) |
Primary outcome
Change in Monthly Migraine Days (MMD)
Time frame: Baseline to the last four weeks of the double-blind treatment phase
Change in MMD from baseline to the last four weeks of the double-blind treatment phase. Migraine days are defined according to ICHD-3 criteria or the use of migraine-specific acute medication, recorded in a daily, electronic diary.
33 secondary outcomes
Responder rate (proportion of participants achieving ≥50% reduction in MMD)
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Change in number of moderate/severe headache days
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Headache severity
Time frame: The last four weeks of the double-blind treatment phase.
Changes in acute medication use.
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Migraine Disability Assessment Scale (MIDAS)
Time frame: Baseline to the end of the double-blind treatment phase (week 12).
Headache Impact Test - 6 items (HIT-6)
Time frame: Baseline to the end of the double-blind treatment phase (week 12).
Work Productivity and Activity Impairment (WPAI)
Time frame: Baseline to the end of the double-blind treatment phase (week 12).
Patient's Global Impression of Change (PGIC)
Time frame: The end of the double-blind treatment phase (Week 12)
Safety and tolerability of cabergoline (incidence of adverse events)
Time frame: From the beginning of the treatment phase (week 0) until the end of the safety follow-up (week 28).
Sustained effect of cabergoline treatment in change in MMD.
Time frame: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effect of cabergoline on responder rate (defined as the proportion of participants achieving a ≥50% reduction in monthly migraine days).
Time frame: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline on the frequency of moderate/severe headache days.
Time frame: Baseline to the last four weeks of the open-label phase, and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on acute medication use.
Time frame: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on HIT-6 score.
Time frame: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on MIDAS score.
Time frame: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on WPAI score.
Time frame: Baseline to the last four weeks of the open-label phase, and the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
Sustained effects of cabergoline treatment on PGIC.
Time frame: The end of the double-blind phase (week 12) and the end of the open-label phase (week 24).
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on MMD
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on responder rate
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on number of moderate/severe headache days
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on acute medication use
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on HIT-6
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on MIDAS
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on WPAI
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Comparison of any treatment (0.5 mg or 1.0 mg) versus placebo on PGIC
Time frame: The end of the double-blind treatment phase (week 12).
Dose-Response Analysis of Change in Monthly Migraine Days (MMD)
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of ≥50% Responder Rate in Monthly Migraine Days.
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Moderate/Severe Headache Days
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Acute Migraine Medication Use
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of HIT-6 Total Score
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of MIDAS Total Score
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Total WPAI (Migraine) Score
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Dose-Response Analysis of Patient Global Impression of Change (PGIC)
Time frame: Baseline to the last four weeks of the double-blind treatment phase.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Background: PubMed 40168298Hjelholt 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) will be shared with researchers upon reasonable request, including baseline characteristics, outcome measures, and adverse events. Data will be available upon publication of the primary manuscript and for a minimum of 5 years. Requests should be directed to the Principal Investigator at ajh@clin.au.dk. Access will be granted upon approval of a data sharing agreement
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabergoline 0.5 MG and Cabergoline 1 MG in people with Migraine, run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Astrid Hjelholt, M.D., Ph.D. (004524800664, ajh@clin.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Monthly Migraine Days (MMD) (time frame: Baseline to the last four weeks of the double-blind treatment phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07072910, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.