| Conditions: |
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Migraine With Aura - Patent Foramen Ovale |
| Purpose: |
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The purpose of the study is to compare the rate of comorbidities associated with migraine
aura 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 migraine with aura 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 migraine with aura 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.
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| Study Summary: |
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A two-group observational study will be performed to determine if comorbidities associated
with migraine aura 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 migraine
aura, 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 TCD.bubble test.. Subjects will also be screened for arterial
variations ("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 CO2 stimulation to assess cerebral vasomotor reactivity..A blood
specimen will be collected to assess three platelet activation biomarkers including CD40
ligand, 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:
- Does the presence of a large PFO have any impact on cognitive function, particularly in
brain regions supplied by posterior circulation, in migraine aura?
- Does cerebral vasomotor reactivity differ between migraineurs with aura, with and
without large PFO?
- Do migraineurs with aura and large PFO have higher biomarkers of platelet activation
(soluble P-selectin, sCD40L, TXB2) than migraineurs with aura without PFO?
- Are there differences in the prevalence and severity of sleep apnea, as assessed by
apnea-hypopnea index (AHI), in migraine aura, with and without large PFO?
- What is the effect of large PFO on monthly migraine frequency (MMF) and aura frequency?
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| Criteria: |
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Inclusion Criteria:
1. Age 18-55 years
2. Ability to speak, read, and understand English
3. Documented diagnosis of migraine with aura for a ≥2 year period preceding enrollment,
confirmed by a neurology healthcare provider (MD, DO, ARNP, PA-C) using the
International Classification of Headache Disorders criteria. Focal neurologic
symptoms must precede or accompany the headache (aura) for at least one headache in
the 12 months prior to enrollment.
4. Average of 4 to 14 migraine days per month for the 3-month period preceding
enrollment
5. Migraine prevention regimen stable for at least 30 days prior to enrollment. This
criterion does not pertain to acute medications or aspirin- or non-steroidal
anti-inflammatory (NSAID)- containing medications, which will be held (wash-out)
prior to blood draw. See below.
6. Able and willing to complete a washout of aspirin, NSAIDs (including ibuprofen,
naproxen sodium, ketorolac), combination drugs containing these compounds, or dietary
supplements containing willow bark (salicylate) prior to blood collection.
7. Experimental group: Documented large right-to-left shunt (RLS) with >100 embolic
tracks (ET) at rest or following calibrated or uncalibrated respiratory strain by TCD
(whichever yields largest number of ET).
8. Control group: Documented absence of right-to-left shunt (RLS) with <11 ET at rest
and following calibrated and uncalibrated respiratory strain by TCD (whichever yields
largest number of ET).
9. Adequate correction of hearing and/or vision deficits
Exclusion Criteria:
1. Pregnancy
2. Postmenopausal female
3. Documented right-to-left shunt (RLS) with 11 to 100 ET at rest or following
calibrated or uncalibrated respiratory strain by TCD (whichever yields largest number
of ET)
4. History of stroke or neurological condition associated with cognitive dysfunction
such as multiple sclerosis, epilepsy, brain tumor or brain injury
5. Chronic migraine or medication overuse headache
6. Prescription use of warfarin or antiplatelet drug such as clopidogrel or aspirin
7. Inability or unwillingness to complete a washout of aspirin, non-steroidal
anti-inflammatory drugs (NSAIDs), combination drugs containing these compounds, or
dietary supplements containing willow bark (salicylate)
8. Evidence of carotid, vertebral, or basilar artery stenosis >50% on duplex imaging
9. Evidence of fetal origins or >50% stenosis of intracranial blood vessels on TCD
imaging
10. Inadequate temporal bone windows (signals) for TCD insonation
11. Daily treatment regimen includes topiramate and/or other medication that causes
significant cognitive or psychomotor impairment based on provider assessment and/or
self-report (e.g., amitryptiline, divalproex sodium)
12. Use of continuous positive-airway pressure (CPAP) instrumentation within 6 months of
study enrollment
13. Status post PFO or RLS closure/repair
14. Beck Depression Inventory score ≥29
15. State-Trait Anxiety Inventory score exceeding cutoff for age and sex
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| NCT ID: |
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NCT01257880 |
| Primary Contact: |
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Principal Investigator
Jill T. Jesurum, Ph.D.
Swedish Medical Center
Jill T. Jesurum, Ph.D.
Phone: 206-386-6290
Email: jill.jesurum@swedish.org
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| Backup Contact: |
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Email: cindy.fuller@swedish.org
Cindy J. Fuller, Ph.D.
Phone: 206-215-2028
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| Location Contact: |
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Seattle, Washington 98195
United States
Sylvia M. Lucas, M.D., Ph.D.
Phone: 206-598-6950
Email: lucass@uw.edu
Site Status: Recruiting |