Migraine Headaches Elimination With Patent Foramen Ovale-Directed Therapy
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-55
SponsorColumbia University
About this trial
Migraine is a common and often disabling condition, but its exact causes are not fully understood. Some people with migraines have a small opening in the heart wall called a patent foramen ovale (PFO). In some of these patients, closing this opening or taking a medication that inhibits blood platelets (prasugrel) has been shown to reduce migraines. However, not everyone benefits, and it is unclear why. This study is being done to better understand whether closing a PFO can provide lasting migraine relief - especially in patients whose migraines improve with prasugrel.
The goal of this study is to find out whether, in patients whose migraines improve while taking prasugrel, closing the PFO along with 24 weeks of prasugrel leads to better long-term migraine relief after stopping the medication, than by taking prasugrel for 24 weeks alone.
Participants will track their migraines daily using an electronic diary, then take prasugrel and compare their migraines while on the medication. Only patients whose migraines improve on this medication will continue in the study. Eligible participants will be randomly assigned (like flipping a coin) to one of two groups: 1) Medication-only group: Continue prasugrel for 24 weeks. 2) Procedure group: Undergo a minimally invasive procedure to close the PFO and continue prasugrel for 24 weeks. After treatment, the medication will be stopped in both groups, and participants will again track their migraines for about 8 weeks.
The main question is: Do patients who have PFO closure continue to have fewer migraines after stopping prasugrel compared with those who did not have the procedure?
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: ≥18 and <55 at time of screening
Migraine headache with aura, or migraine headache without aura, fulfilling conditions of the Neurology Screening Tool (meeting ICHD-3 criteria)
Diagnosis of migraine for ≥ 1 year; onset of migraine symptoms < 40 years of age
without current preventative therapy, OR
Disqualifiers
Headache disorder other than migraine with aura, or migraine without aura
Patient has history of stroke, TIA, or intracranial hemorrhage.
Patient has a history of thrombocytopenia within one year, or platelet count <100,000/mm3 identified during the screening laboratory evaluation.
Patient has severe hepatic impairment with reduced synthetic function as documented by prolongation of PT/PTT, or with total bilirubin >3.0 mg/dL identified during the screening laboratory evaluation.
Trial design
Design model
Parallel
Treatments tested in this trial
Prasugrel 5mg
DrugSix months of daily prasugrel therapy following randomization.
Transcatheter Closure of Patent Foramen Ovale
DeviceA standard transcatheter closure of PFO will be performed in the Group B cohort. During this non-surgical procedure, the GORE Cardioform Septal Occluder will be used to close the PFO (it is FDA-approved for exactly this purpose for prevention of recurrent stroke) but will be used here in an off-label fashion.
Treatment groups
32 Participants
are divided into 2 treatment groupsGroup A: Group A - Thienopyridine onlyActive comparator 1 intervention
Group B: Group B - PFO closure plus thienopyridineActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Reduction in Monthly Migraine Days (MMD)
The primary efficacy endpoint is the proportion of randomized subjects maintaining a clinically meaningful migraine response, defined as a ≥50% reduction in Monthly Migraine Days (MMD) in the Post-Therapy monitoring session, compared with the Baseline monitoring session (following discontinuation of prasugrel).
Time frame
upon completion of the 56-day Post-Therapy monitoring sessionSecondary outcomes
1
Effect Persistence (EP)
Effect Preservation (EP) is a constructed metric which defines the extent to which the clinical benefit of migraine reduction observed during thienopyridine therapy is maintained following discontinuation of therapy. EP is calculated for each randomized subject as the proportion of the On-Therapy reduction in Monthly Migraine Days (MMD) that is preserved during the Post-Therapy period, expressed as a percentage. For each subject, EP is defined as: EP = (Post-Therapy Reduction in MMD / On-Therapy Reduction in MMD) × 100 where: Post-Therapy Reduction in MMD = Baseline MMD - Post-Therapy MMD On-Therapy Reduction in MMD = Baseline MMD - On-Therapy MMD EP provides a continuous, subject-level measure of treatment durability, allowing comparison of the extent to which the initial treatment effect is maintained following therapy discontinuation.
Time frame
upon completion of the 56-day Post-Therapy monitoring session2
Responder-based Endpoints
Responder-based endpoints will assess higher thresholds of clinical response and will include the proportion of subjects achieving: * ≥75% reduction in MMD from Baseline during the Post-Therapy monitoring period * ≥90% reduction in MMD from Baseline, representing near complete elimination of migraine days * 100% reduction in MMD from Baseline, representing complete elimination of migraine days.
Time frame
upon completion of the 56-day Post-Therapy monitoring session3
Absolute reduction in MMD from Baseline to Post-Therapy
This measure will calculate the absolute difference in MMD between the Baseline monitoring session and the Post-Therapy monitoring session.
Time frame
upon completion of the 56-day Post-Therapy monitoring session4
Percent reduction in MMD from Baseline to Post-Therapy
This measure will assess the percentage difference in MMD between the Baseline monitoring session and the Post-Therapy session.
Time frame
upon completion of the 56-day Post-Therapy monitoring sessionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Columbia University
Lead sponsor
Occlutech International AB
Collaborator
W.L.Gore & Associates
Collaborator
Source ClinicalTrials.gov