Prevention and Treatment of Episodic Migraine by Cabergoline Therapy (PROTECT). A Randomized, Placebo-controlled, Double-blind, Investigator-initiated Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in Monthly Migraine Days (MMD)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •< 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
研究组 & 干预措施
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.
干预措施: Cabergoline 0.5 MG (Drug)
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.
干预措施: Cabergoline 1 MG (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Monthly Migraine Days (MMD)
时间窗: 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.
次要结局
- 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).)
- Headache Impact Test - 6 items (HIT-6)(Baseline to the end of the double-blind treatment phase (week 12).)
- Work Productivity and Activity Impairment (WPAI)(Baseline to the end of the double-blind treatment phase (week 12).)
- Patient's Global Impression of Change (PGIC)(The end of the double-blind treatment phase (Week 12))
- Safety and tolerability of cabergoline (incidence of adverse events)(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.(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).(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.(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.(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.(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.(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.(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.(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(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(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(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(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(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(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(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(The end of the double-blind treatment phase (week 12).)
- Dose-Response Analysis of Change in Monthly Migraine Days (MMD)(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of ≥50% Responder Rate in Monthly Migraine Days.(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of Moderate/Severe Headache Days(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of Acute Migraine Medication Use(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of HIT-6 Total Score(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of MIDAS Total Score(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of Total WPAI (Migraine) Score(Baseline to the last four weeks of the double-blind treatment phase.)
- Dose-Response Analysis of Patient Global Impression of Change (PGIC)(Baseline to the last four weeks of the double-blind treatment phase.)