An observational study in Migraine With Aura and Patent Foramen Ovale, sponsored by Swedish Medical Center. Completed at 2 sites in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2011-09-27.
Sponsored by Swedish Medical Center · Observational
The purpose of the study is to compare the rate of comorbidities associated with migraine aura (MA) between persons who have a large circulatory right-to-left shunt (RLS) and those who do not have RLS.
Approximately 50% of individuals who have MA also have RLS due to patent foramen ovale (PFO). A PFO is an anatomical opening or flap between the upper chambers of the heart or atria that permits blood to pass from the right of the heart to the left side of the heart, without first going to the lungs to be filtered and oxygenated. Many health conditions and clinical syndromes including stroke, sleep apnea, and migraine have been linked to PFO. Although the mechanism is undetermined, it is hypothesized that microscopic blood clots and chemicals such as serotonin can pass through the PFO, travel to the brain, and cause headache and aura.
Persons who have MA are at increased risk for stroke and transient ischemic attacks relative to people who do not have migraine. Migraine is also associated with the presence of white matter lesions in the brain and mild deficits in cognitive function associated with the posterior brain (vision, memory, processing speed). The risk of stroke in migraine is highest for women under the age of 45 who have aura and a high number of migraine headache days per month. No convincing evidence has been produced to explain the mechanism for the increased risk of ischemic stroke in migraine; however, increased platelet activation and aggregation is a plausible theory.
We hypothesize that migraineurs with aura and large RLS (presumably due to a PFO) will be more likely to have sleep apnea, increased platelet activation, cognitive deficits, alterations in cerebral vasomotor function, and white matter lesions than migraineurs with aura who do not have PFO. The results of this exploratory study will generate hypotheses as to why subgroups of migraineurs have an increased risk of stroke and the impact of large PFO on comorbid conditions associated with migraine aura. Early identification of migraine subgroups with a constellation of clinical syndromes that increase risk of neurovascular diseases will allow initiation of preventive strategies that may ultimately reduce burden and improve the productive quality of life for these individuals.
A two-group observational study will be performed to determine if comorbidities associated with MA are more prevalent in the setting of large PFO. Potential subjects will be screened to assure that initial inclusion criteria are met (age, diagnosis of MA, monthly migraine frequency). Those who meet criteria will complete questionnaires including general medical history, migraine and aura frequencies, migraine-related disability, and treatment and preventive medications. In addition, subjects will be asked to complete two surveys on insomnia and sleep quality. Presence or absence of large PFO will be assessed by transcranial Doppler (TCD) bubble test. Subjects will also be screened for arterial variations in the Circle of Willis ("fetal origins") and carotid artery stenosis by duplex ultrasound examination of the arteries of the head and neck. If a subject is found to have a small-to-medium PFO on TCD evaluation, fetal origins, or carotid artery stenosis, s/he will be excluded from remaining study procedures.
Subjects who have either a large PFO or no PFO will undergo measurement of brain blood flow dynamics using TCD and carbon dioxide (CO2) stimulation to assess cerebral vasomotor reactivity. A blood specimen will be collected to assess three platelet activation biomarkers including CD40 ligand (sCD40L), P-selectin, and thromboxane B2 (TXB2). Subjects will be screened for sleep apnea using a portable sleep monitor for home use; results will be analyzed by a sleep medicine specialist. Finally, each subject will undergo a battery of performance -based cognitive function tests that measure visual and auditory memory, processing speed, attention, and eye-hand coordination. If magnetic resonance imaging (MRI) evaluation has been performed within the past 5 years, the film will be reviewed by a neuroradiologist to assess the presence of white matter lesions. Additional MRI will not be performed as part of the study. Completion of the study will necessitate up to three clinic visits (total 5-6 hours) and the home sleep study.
The research questions are as follows:
1,528 studies on the registry are indexed under Migraine Disorders; 299 are open to participants now.
This study's enrollment of 31 is below the median of 130 across 299 observational studies indexed under Migraine Disorders.
Browse Migraine Disorders studies →Swedish Medical Center is the lead sponsor of 40 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Otherwise healthy persons who have a diagnosis of MA, based on the International Classification of Headache Disorders Diagnostic Criteria, will be recruited from headache and neurology clinics. Potential subjects can self refer if they have a diagnosis of MA.
Exclusion Criteria:
Persons who have migraine aura and no evidence of PFO, based on transcranial Doppler evaluation.
Persons who have migraine aura and large PFO, as assessed by transcranial Doppler evaluation.
Embolic Tracks
Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver
Time frame: Baseline
Cerebral Vasomotor Reactivity (VMR)
The percentage change in basilar artery blood flow velocity from baseline between hypercapnia (increased blood CO2) and hypocapnia (decreased blood CO2), as measured by transcranial Doppler during a single testing period. This is calculated using the following equation: VMR = 100 x (VelocityHYPERCAPNIA - VelocityHYPOCAPNIA) / VelocityBASELINE
Time frame: Baseline
Platelet Activation
Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.
Time frame: Baseline
Sleep Apnea, Number of Participants
An apnea-hypopnea index (AHI) \>10 per hour during a home sleep study, defined as at least 5 hours of recorded data on the portable sleep monitor instrument for either the apnea-hypopnea index (AHI) or oxygen desaturation index (ODI) and at least 3 hours for the other index. The scale adopted for assessment of sleep apnea is as follows: AHI \< 5, optimal; AHI 5-10, equivocal, participant may have sleep apnea; AHI \>10, sleep apnea highly likely.
Time frame: Following one night of a home sleep study
Cognitive Function
Cognitive function will be assessed by a battery of performance-based neuropsychological tests.
Time frame: Baseline
Oxygen Desaturation Index
Measurement of number of times per hour blood oxygen saturation decreases by at least 4% during home sleep study.
Time frame: Baseline
White Matter Lesions
Presence and severity of white matter lesions on magnetic resonance imaging, taken within 5 years prior to study enrollment. Subjects will not have magnetic resonance imaging performed as part of this study. Films will be requested and an independent neuroradiologist will assess presence of white matter lesions.
Time frame: Within 5 years prior to enrollment
Over a 20-month period (January 2010 to May 2011), 127 subjects were screened and 31 were enrolled from Swedish Medical Center and the University of Washington Medical Center, including 19 with MA + PFO and 12 with MA - PFO.
| Milestone | Control (Absence of PFO) | Large PFO |
|---|---|---|
| Started | 12 | 19 |
| Completed | 12 | 19 |
| Not completed | 0 | 0 |
Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver
Results for this outcome have not been posted.
The percentage change in basilar artery blood flow velocity from baseline between hypercapnia (increased blood CO2) and hypocapnia (decreased blood CO2), as measured by transcranial Doppler during a single testing period. This is calculated using the following equation: VMR = 100 x (VelocityHYPERCAPNIA - VelocityHYPOCAPNIA) / VelocityBASELINE
| Percentage change | Control (Absence of PFO) | Large PFO |
|---|---|---|
| Cerebral Vasomotor Reactivity (VMR) | 89 ± 20 | 97 ± 24 |
Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.
Results for this outcome have not been posted.
An apnea-hypopnea index (AHI) \>10 per hour during a home sleep study, defined as at least 5 hours of recorded data on the portable sleep monitor instrument for either the apnea-hypopnea index (AHI) or oxygen desaturation index (ODI) and at least 3 hours for the other index. The scale adopted for assessment of sleep apnea is as follows: AHI \< 5, optimal; AHI 5-10, equivocal, participant may have sleep apnea; AHI \>10, sleep apnea highly likely.
| participants | Control (Absence of PFO) | Large PFO |
|---|---|---|
| Sleep Apnea, Number of Participants | 0 | 1 |
Cognitive function will be assessed by a battery of performance-based neuropsychological tests.
Results for this outcome have not been posted.
Measurement of number of times per hour blood oxygen saturation decreases by at least 4% during home sleep study.
Results for this outcome have not been posted.
Presence and severity of white matter lesions on magnetic resonance imaging, taken within 5 years prior to study enrollment. Subjects will not have magnetic resonance imaging performed as part of this study. Films will be requested and an independent neuroradiologist will assess presence of white matter lesions.
Results for this outcome have not been posted.
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Control (Absence of PFO) | — | 0/12 (0%) | 0/12 (0%) |
| Large PFO | — | 0/19 (0%) | 0/19 (0%) |
| Age, Categorical(Participants) | Control (Absence of PFO) | Large PFO | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 12 | 19 | 31 |
| >=65 years | 0 | 0 | 0 |
| Age Continuous(years) | Control (Absence of PFO) | Large PFO | Total |
|---|---|---|---|
| Mean | 37 ± 10 | 35 ± 11 | 35 ± 11 |
| Sex: Female, Male(Participants) | Control (Absence of PFO) | Large PFO | Total |
|---|---|---|---|
| Female | 11 | 16 | 27 |
| Male | 1 | 3 | 4 |
| Region of Enrollment(participants) | Control (Absence of PFO) | Large PFO | Total |
|---|---|---|---|
| United States | 12 | 19 | 31 |
This study is completed, as verified in Sep 2011. You cannot join it, but the record below documents what was studied.
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