Cabergoline for Episodic Migraine

NCT07072910 | Recruiting Phase 2 DMC

• 2 other identifiers: AU-PROTECT-20252025-522323-10-00
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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. 1.Does once-weekly cabergoline (0.5 mg or 1.0 mg) reduce MMD compared to placebo?
2. 2.What are the effects of cabergoline on headache severity, acute medication use, and patient-reported outcomes?
3. 3.Is cabergoline safe to use in individuals with migraine?
4. 4.Cabergoline 0.5 mg/week
5. 5.Cabergoline 1.0 mg/week
6. 6.Placebo

Conditions

Migraine

Keywords

Migraine; Preventive treatment; Cabergoline; Drug repurposing

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  Baseline to the last four weeks of the double-blind treatment phase.

• Change in number of moderate/severe headache days

  Baseline to the last four weeks of the double-blind treatment phase.

• Headache severity

  The last four weeks of the double-blind treatment phase.

• Changes in acute medication use.

  Baseline to the last four weeks of the double-blind treatment phase.

• Migraine Disability Assessment Scale (MIDAS)

  Baseline to the end of the double-blind treatment phase (week 12).

Other Outcomes (14)

• Pharmacogenetic predictors of treatment response.

  Baseline

• Cost-effectiveness.

  Baseline to the end of the double-blind phase (week 12) and the end of the the open-label phase (week 24).

• Change in serum prolactin.

  Baseline to the end of the double-blind phase (week 12) and the end of the the open-label phase (week 24).

Study Arms (3)

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.

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.

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.

Drug: Placebo

Interventions

Cabergoline 0.5 MG 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.

Also known as: Dopamine receptor agonist, Dostinex

Cabergoline 0.5 mg/Week (Double-Blind Phase)

Placebo 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.

Placebo (Double-Blind Phase)

Cabergoline 1 MG 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.

Also known as: Dopamine receptor agonist, Dostinex

Cabergoline 1.0 mg/Week (Double-Blind Phase)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Episodic migraine according to ICHD-3 criteria
• Written informed consent

You may not qualify if:

• \< 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
• 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

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Aarhus University Hospital

Aarhus N, 8200, Denmark

RECRUITING

Related Publications (1)

• 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.

  PMID: 40168298 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders

Interventions

Cabergoline; Dopamine Agonists

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Central Study Contacts

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

CONTACT

004524800664; ajh@clin.au.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: July 18, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: De-identified individual participant data (IPD) and supporting information will be available upon publication of the primary manuscript and for a minimum of 5 years thereafter.
• Access Criteria: Access to IPD and supporting documents will be granted to qualified researchers upon reasonable request, subject to approval of a data sharing agreement. Requests should be directed to the Principal Investigator at ajh@clin.au.dk. Researchers must provide a sound scientific proposal and agree to use the data only for the purpose described in the approved data sharing agreement.

Locations

DK (1)