Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP) (CAMP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01257880|
Recruitment Status : Completed
First Posted : December 10, 2010
Results First Posted : September 21, 2011
Last Update Posted : September 27, 2011
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.
|Condition or disease|
|Migraine With Aura Patent Foramen Ovale|
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 Type :||Observational|
|Actual Enrollment :||31 participants|
|Observational Model:||Case Control|
|Official Title:||Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||May 2011|
|Actual Study Completion Date :||May 2011|
Control (absence of PFO)
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 [ 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.
- Oxygen Desaturation Index [ Time Frame: Baseline ]Measurement of number of times per hour blood oxygen saturation decreases by at least 4% during home sleep study.
- White Matter Lesions [ Time Frame: Within 5 years prior to enrollment ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01257880
|United States, Washington|
|Swedish Medical Center|
|Seattle, Washington, United States, 98122|
|The University of Washington|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Jill T. Jesurum, Ph.D.||Swedish Medical Center|
|Principal Investigator:||Cindy J. Fuller, Ph.D.||Swedish Medical Center|
|Study Chair:||Sylvia M. Lucas, M.D., Ph.D.||University of Washington|
|Study Chair:||Natalia Murinova, M.D.||University of Washington|
|Study Chair:||Alan M. Haltiner, Ph.D.||Swedish Medical Center|
|Study Chair:||Colleen M. Douville, B.S.||Swedish Medical Center|