Clinical Trial: Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)

Brief 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). 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

Detailed Summary:

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. Addition
Sponsor: Swedish Medical Center

Current 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 neuropsycholog

    Original Primary Outcome:

    • Embolic Tracks [ Time Frame: Baseline ]
      Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver
    • Cerebral vasomotor reactivity [ Time Frame: Baseline ]
      The percent change in cerebral vessel blood velocity from baseline between hypercapnia and hypocapnia. This will be calculated for both middle cerebral arteries and the basilar artery.
    • Platelet Activation [ Time Frame: Baseline ]
      Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.
    • Sleep apnea [ Time Frame: Baseline ]
      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 ours for the other index.
    • Cognitive Function [ Time Frame: Baseline ]
      Cognitive function will be assessed by a battery of performance-based neuropsychological tests.


    Current Secondary Outcome:

    • 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.


    Original Secondary Outcome: Same as current

    Information By: Swedish Medical Center

    Dates:
    Date Received: December 8, 2010
    Date Started: January 2010
    Date Completion:
    Last Updated: September 21, 2011
    Last Verified: September 2011