Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP)

NCT01257880 | Completed Results

• 1 other identifier: 4865S-09
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 2

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 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.

Conditions

Migraine With Aura; Patent Foramen Ovale

Keywords

Migraine; Migraine with Aura; Aura; Patent Foramen Ovale; Platelets; Sleep Apnea; Cognitive Function

Outcome Measures

Primary Outcomes (5)

• Embolic Tracks

  Embolic tracks on transcranial Doppler at rest and following calibrated Valsalva maneuver

  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

  Baseline

• Platelet Activation

  Platelet-poor plasma levels of sCD40L and P-selectin, and serum concentration of TXB2.

  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.

  Following one night of a home sleep study

• Cognitive Function

  Cognitive function will be assessed by a battery of performance-based neuropsychological tests.

  Baseline

Secondary Outcomes (2)

• Oxygen Desaturation Index

  Baseline

• White Matter Lesions

  Within 5 years prior to enrollment

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Swedish Medical Center: lead
• University of Washington: collaborator
• Coherex Medical: collaborator
• The John L. Locke, Jr. Charitable Trust: collaborator
• National Headache Foundation: collaborator

Study Sites (2)

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

The University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Migraine with Aura; Foramen Ovale, Patent; Migraine Disorders; Epilepsy; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Limitations and Caveats

Subjects were recruited from a headache clinic and had a high degree of migraine burden; thus, the sample may not accurately represent the general migraine population. The number of men in the sample was insufficient to test sex differences.

Results Point of Contact

• Title: Jill T. Jesurum, Ph.D.
• Organization: Swedish Medical Center

jill.jesurum@swedish.org

206-683-1505

Study Officials

• Jill T. Jesurum, Ph.D.

  Swedish Medical Center

  PRINCIPAL INVESTIGATOR

• Cindy J. Fuller, Ph.D.

  Swedish Medical Center

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2010
• First Posted: December 10, 2010
• Study Start: January 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: September 27, 2011
• Results First Posted: September 21, 2011

Record last verified: 2011-09

Locations

US (2)