Migraine With AuraCAMPNCT01257880
Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)
An observational study of Migraine With Aura and Patent Foramen Ovale, run by Swedish Medical Center at 2 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Migraine With Aura, Patent Foramen Ovale
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2010to May 2011
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: 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.
Who may be able to join
- Age 18-55 years
- Ability to speak, read, and understand English
- Documented diagnosis of migraine aura (MA) 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.
- Average of 4 to 14 migraine days per month for the 3-month period preceding enrollment
- 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.
- 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.
Show all 9Show fewer
- 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).
- 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).
- Adequate correction of hearing and/or vision deficits
Who cannot join
- Pregnancy
- Postmenopausal female
- 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)
- History of stroke or neurological condition associated with cognitive dysfunction such as multiple sclerosis, epilepsy, brain tumor or brain injury
- Chronic migraine or medication overuse headache
- Prescription use of warfarin or antiplatelet drug such as clopidogrel or aspirin
Show all 15Show fewer
- 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)
- Evidence of carotid, vertebral, or basilar artery stenosis >50% on duplex imaging
- Evidence of fetal origins or >50% stenosis of intracranial blood vessels on TCD imaging
- Inadequate temporal bone windows (signals) for TCD insonation
- 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)
- Use of continuous positive-airway pressure (CPAP) instrumentation within 6 months of study enrollment
- Status post PFO or RLS closure/repair
- Beck Depression Inventory score ≥29
- State-Trait Anxiety Inventory score exceeding cutoff for age and sex
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Swedish Medical Center
Seattle, Washington, 98122
The University of Washington
Seattle, Washington, 98195
About this study
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.
Read more
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.
Read the detailed description
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:
- 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?
- Conditions
- Migraine With Aura, Patent Foramen Ovale
- Keywords
- Migraine, Migraine with Aura, Aura, Patent Foramen Ovale, Platelets, Sleep Apnea, Cognitive Function
- Medical subject headings
- Migraine with Aura, Foramen Ovale, Patent, Migraine Disorders, Epilepsy, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control (absence of PFO) | Persons who have migraine aura and no evidence of PFO, based on transcranial Doppler evaluation. | |
| Large PFO | Persons who have migraine aura and large PFO, as assessed by transcranial Doppler evaluation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Embolic Tracks
Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver
Measured: 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
Measured: Baseline
Platelet Activation
Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.
Measured: 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.
Measured: Following one night of a home sleep study
Cognitive Function
Cognitive function will be assessed by a battery of performance-based neuropsychological tests.
Measured: Baseline
Secondary outcomes (2)
Oxygen Desaturation Index
Measurement of number of times per hour blood oxygen saturation decreases by at least 4% during home sleep study.
Measured: 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.
Measured: Within 5 years prior to enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2010 (estimated)
- Study startJan 2010
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Migraine With AuraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington, Coherex Medical, The John L. Locke, Jr. Charitable Trust, National Headache Foundation
- Responsible party
- Sponsor
- Investigators
- Jill T. Jesurum, Ph.D., Principal investigator, Swedish Medical CenterCindy J. Fuller, Ph.D., Principal investigator, Swedish Medical CenterSylvia M. Lucas, M.D., Ph.D., Study chair, University of WashingtonNatalia Murinova, M.D., Study chair, University of WashingtonAlan M. Haltiner, Ph.D., Study chair, Swedish Medical CenterColleen M. Douville, B.S., Study chair, Swedish Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01257880
- Sponsor's protocol ID
- 4865S-09
- Acronym
- CAMP
- Status last verified
- Sep 2011
- First submitted
- 8 Dec 2010
- Last updated
- 27 Sep 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)
- ClinicalTrials.gov ID
- NCT01257880
- Acronym / sponsor ID
- CAMP / 4865S-09
- Conditions
- Migraine With Aura, Patent Foramen Ovale
- Keywords
- Migraine, Migraine with Aura, Aura, Patent Foramen Ovale, Platelets, Sleep Apnea, Cognitive Function
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Swedish Medical CenterUniversity, hospital or other
- Collaborators
- University of Washington, Coherex Medical, The John L. Locke, Jr. Charitable Trust, National Headache Foundation
- Study start
- Jan 2010
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 10 Dec 2010 (estimated)
- Results
- Posted 21 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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?
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control (absence of PFO) | – | –Persons who have migraine aura and no evidence of PFO, based on transcranial Doppler evaluation. |
| Large PFO | – | –Persons who have migraine aura and large PFO, as assessed by transcranial Doppler evaluation. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- 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.
Key inclusion criteria (9 listed)
- Age 18-55 years
- Ability to speak, read, and understand English
- Documented diagnosis of migraine aura (MA) 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.
- Average of 4 to 14 migraine days per month for the 3-month period preceding enrollment
- 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.
Key exclusion criteria (15 listed)
- Pregnancy
- Postmenopausal female
- 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)
- History of stroke or neurological condition associated with cognitive dysfunction such as multiple sclerosis, epilepsy, brain tumor or brain injury
- Chronic migraine or medication overuse headache
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Embolic Tracks
Time frame: Baseline
Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver
Cerebral Vasomotor Reactivity (VMR)
Time frame: Baseline
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
Platelet Activation
Time frame: Baseline
Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.
Sleep Apnea, Number of Participants
Time frame: Following one night of a home sleep study
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.
Cognitive Function
Time frame: Baseline
Cognitive function will be assessed by a battery of performance-based neuropsychological tests.
2 secondary outcomes
Oxygen Desaturation Index
Time frame: Baseline
White Matter Lesions
Time frame: Within 5 years prior to enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jill T. Jesurum, Ph.D. principal investigator
Swedish Medical Center
Cindy J. Fuller, Ph.D. principal investigator
Swedish Medical Center
Sylvia M. Lucas, M.D., Ph.D. study chair
University of Washington
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine With Aura and Patent Foramen Ovale, run by Swedish Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Embolic Tracks (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2011.