Headache, Migraine, Migraine Headache
Conditions
Keywords
headache, chronic, migraine, right to left shunt
Brief summary
This is a prospective, open-label, single-arm pilot study treating 40 subjects to assess the hypothesis that P2Y, G protein-coupled 12 (P2Y12) inhibition with Brilinta/ticagrelor (90 mg by mouth (PO) twice a day) reduces episodic and/or chronic migraine headache symptoms in patients with right to left shunt. Headache frequency while on Brilinta/ticagrelor will be compared with the documented baseline for each subject. If the Brilinta/ticagrelor therapy was effective (\> 50% reduction in monthly headache days), the subject could elect to continue therapy for an additional two months (56 days), while continuing to complete daily headache logs.
Detailed description
Migraine headaches are poorly understood, and can be severely debilitating. Many types of drugs have been tried in migraine sufferers including anti-depressants, anti-seizure medications, blood pressure medicines and others. The investigators have shown that in a small number of patients, a certain type of blood thinner (Clopidogrel) can reduce or eliminate migraine headaches in patients who also have a hole in the heart wall that allows flow from the right side of the heart to the left. Ticagrelor is a blood thinning drug which works in the same way as the clopidogrel, but is broken down by the body differently and thus allows everyone to use it. The investigators wish to test this medication to see if it works as well, or better than the clopidogrel.
Interventions
DRUGTicagrelor 90 mg twice per day
Patients will be loaded with 180 mg of Ticagrelor during the enrollment office visit and provided with a 28 day supply of Ticagrelor, 90 mg twice per day. P2Y12 reactivity unit (PRU) testing will be conducted at 7-14 days. If the patient has a positive response, they will have the option of continued access of Ticagrelor 180 mg for another 2 months. Participants will be reminded via text message daily to complete a headache survey on line in order to track their headaches.
Sponsors
AstraZeneca
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* At least one year history of Episodic or Chronic migraine headache symptoms * At least 6 headache days per month * Subject able to complete online daily headache log
Exclusion criteria
* Inability to understand the study or history of non-compliance with medical advice * Currently taking a P2Y12 inhibitor * Known hypersensitivity to Brilinta/ticagrelor * History of stroke/transient ischemic attack (TIA) in the previous 6 months * Active bleeding from any site * Active peptic ulcer disease or upper gastrointestinal (GI) bleeding within six (6) months * Migraine onset after 50 years of age * Renal impairment: Creatinine Clearance \< 60 cc/min * Severe hepatic impairment with total bilirubin \> 3.0 mg/dL * Thrombocytopenia with platelet count \< 100,000 / ul * History of intracranial hemorrhage * Contraindications to blood thinner therapy or history of major bleeding episode while taking blood thinner therapy * Need for chronic oral anti-coagulation therapy (i.e. Atrial Fibrillation) * Need for chronic anti-platelet therapy (i.e. drug-eluting (DE) Stent), including daily aspirin use * Need for daily nonsteroidal anti-inflammatory drug (NSAID) use * Need for daily carbamazepine therapy or other strong CYP3A inhibitors or potent CYP3A inducers * Need for simvastatin or lovastatin greater than 40 mg daily * Symptomatic bradycardia or syncope * Pregnancy or currently breast-feeding, or plan to become pregnant during the study period * Planned surgery during the study time-frame * Previously implanted patent foramen ovale (PFO), atrial septal defect (ASD), pacemaker, inferior vena cava filter, or left atrial appendage closure device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Responders | 1 month from baseline | A participant will be considered to have achieved the primary efficacy endpoint (a Responder) if she/he has \>50% reduction in the number of monthly headache days during the month of therapy compared with participant's own baseline. If there is \< 50% reduction in the number of migraine days, she/he will be considered a Non-Responder. |
Countries
United States
Participant flow
Recruitment details
Study subjects were recruited from the hospital-based cardiology and headache clinics at Columbia University Medical Center and through the private offices of the study physicians. All subjects were evaluated by a Neurologist and fulfilled MHA criteria of the International Classification of Headache Disorders (ICHD - 3 Beta).
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor 90 mg Twice Per Day Interventions include the following: All participants will have a loading dose of Ticagrelor (Brilinta) 180 mg administered in the office at the time of enrollment. Thereafter, for 28 days, Ticagrelor 90 mg tablet will be taken once in the morning and once in the evening, as close to 12 hours apart as possible. Each day, the subject will receive a text message reminder to login to the website, to record her/his headache activity.
Ticagrelor 90 mg twice per day: Patients will be loaded with 180 mg of Ticagrelor during the enrollment office visit and provided with a 28 day supply of Ticagrelor, 90 mg twice per day. P2Y12 reactivity unit (PRU) testing will be conducted at 7-14 days. If the patient has a positive response, they will have the option of continued access of Ticagrelor 180 mg for another 2 months. Participants will be reminded via text message daily to complete a headache survey on line in order to track their headaches. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Ticagrelor 90 mg Twice Per Day |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 10 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
Total Number of Responders
A participant will be considered to have achieved the primary efficacy endpoint (a Responder) if she/he has \>50% reduction in the number of monthly headache days during the month of therapy compared with participant's own baseline. If there is \< 50% reduction in the number of migraine days, she/he will be considered a Non-Responder.
Time frame: 1 month from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor 90 mg Twice Per Day | Total Number of Responders | 17 Participants |