Cabergoline for Episodic Migraine (PROTECT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Midtjylland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2025-11-07

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Danish Independent Research Fund, grant ID: 10.46540/4308-00036B

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Prophylaxis

To compare the efficacy of once-weekly cabergoline 0.5 mg and 1.0 mg versus placebo in reducing migraine frequency in patients with episodic migraine.

Secondary objectives 13

1. To compare once-weekly cabergoline 0.5 mg and 1.0 mg versus placebo in achieving ≥50% reduction in MMD.
2. To compare once-weekly cabergoline 0.5 mg and 1.0 mg versus placebo in reducing headache severity and burden.
3. To compare once-weekly cabergoline 0.5 mg and 1.0 mg versus placebo in reducing acute medication use.
4. To compare once-weekly cabergoline 0.5 mg and 1.0 mg versus placebo on patient-reported outcomes.
5. To evaluate sustained effects of cabergoline treatment in the open-label extension phase.
6. To compare any treatment (0.5 mg or 1.0 mg) versus placebo across all primary and secondary efficacy endpoints.
7. To assess potential dose–response relationships across all primary and secondary efficacy endpoints by including all three treatment arms (placebo, cabergoline 0.5 mg, and cabergoline 1.0 mg) in a single model.
8. To assess the safety and tolerability of cabergoline.
9. To assess metabolic and inflammatory markers.
10. To assess change in serum prolactin.
11. To explore treatment effects in relevant subgroups.
12. To explore pharmacogenetic predictors of treatment response
13. To explore cost-effectiveness.

Conditions and MedDRA coding

Migraine

Study design 4 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

Individual participant data will be shared upon reasonable request, subject to approval by the research team and in accordance with GDPR and applicable ethical regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Episodic migraine with or without aura as defined by ICHD, 3rd edition, present for at least 12 months
2. 4–14 MMD in the last 3 months prior to inclusion
3. Male or female subjects ≥18 years of age
4. Written informed consent

Exclusion criteria 17

1. < 4 MMD or ≥ 15 MMD during the baseline period
2. 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)
3. Changes in concomitant migraine-specific treatment within the 3 months prior to inclusion, or any planned adjustments to such treatment during the study period
4. History of pulmonary, retroperitoneal, or pericardial disorders, including heart valve disease
5. Severe untreated hypertension
6. Psychiatric disorders requiring pharmacological treatment
7. Chronic migraine (≥15 headache days per month)
8. Concurrent participation in another clinical trial that, in the judgement of the investigator, may interfere with the conduct or outcomes of the present study
9. Use of drugs with dopamine antagonistic or agonistic properties
10. 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
11. Women who are breast-feeding
12. Known hypersensitivity or allergy to compounds similar to the investigational medicinal product
13. Inability, in the opinion of the investigator, to understand or comply with study medication or procedures, or any condition which, in the investigator’s judgement, may render the subject unable to complete the study
14. Presumed medication-overuse headache (MOH)
15. Trigeminal autonomic cephalalgias and neuralgias
16. Secondary headache conditions
17. Women who have a positive pregnancy test at randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in MMD from baseline to the end of the 12-week double-blind phase. Migraine days are defined according to ICHD-3 criteria or the use of migraine-specific acute medication, recorded in a daily, electronic diary.

Secondary endpoints 16

1. Change in MMD from baseline to the last four weeks of the double-blind treatment phase.
2. Proportion of participants achieving ≥50% reduction in MMD during the last four weeks of the 12-week double-blind treatment phase.
3. Change in number of moderate/severe headache days from baseline to the last four weeks of the double-blind treatment phase.
4. Proportion of attacks classified as mild, moderate, or severe at the last four weeks of the double-blind treatment phase.
5. 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.
6. Change in MIDAS, HIT-6 and WPAI scores from baseline to the last four weeks of the double-blind treatment phase.
7. PGIC score at the end of the double-blind treatment phases.
8. Change in MMD, proportion of participants achieving ≥50% reduction in MMD, number of moderate/severe headache days, acute medication use, and patient-reported outcomes (HIT-6, MIDAS, WPAI, and PGIC) assessed from baseline and from the last four weeks of the double-blind phase to the last four weeks of the open-label phase.
9. Change in MMD, proportion of participants achieving ≥50% reduction in MMD, number of moderate/severe headache days, acute medication use, and patient-reported outcomes (HIT-6, MIDAS, WPAI, and PGIC) from baseline to the last four weeks of the double-blind phase.
10. Change in MMD, proportion of participants achieving ≥50% reduction in MMD, number of moderate/severe headache days, acute medication use, and patient-reported outcomes (HIT-6, MIDAS, WPAI, and PGIC) from baseline to the last four weeks of the double-blind phase.
11. Incidence, severity, and type of AEs and SAEs during the trial.
12. Change in LDL-C, HDL-C, total cholesterol, triglycerides, HbA1c, FSH, LH, estrogen/testosterone, and hs-CRP from baseline to the end of the double-blind and open-label treatment phases.
13. Change in serum prolactin levels from baseline to the end of the double-blind and open-label treatment phases.
14. Genotyping of all participants for variants in the prolactin receptor and dopaminergic pathways previously associated with migraine and drug response.
15. Stratified analyses of efficacy and safety outcomes by sex, menopausal status, aura, presence of dopaminergic symptoms, and number of prior preventive treatments.
16. Estimation of cost per responder and cost per QALY gained. This analysis will be descriptive and exploratory.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus Universitet

Contact name

Astrid Johannesson Hjelholt

Public contact point

Organisation

Aarhus Universitet

Contact name

Astrid Johannesson Hjelholt

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications