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Understanding the Pathophysiology of Migraine Pain

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ClinicalTrials.gov Identifier: NCT03026101
Recruitment Status : Not yet recruiting
First Posted : January 20, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Migraine is the most common headache disorder, prevalent in 18% of females and 6% of males. Emergency room visits, physician consults, hospitalizations, medications, and indirect costs such as lost work days and decreased productivity place the global economic burden of migraines at over 20 billion dollars. It is prevalent in 28 million people in the US alone. Symptoms include unilateral, throbbing, debilitating headache pain accompanied by nausea, vomiting, photophobia, and phonophobia. Upwards of 75% of migraine patients have reduced functionability, have lost time at work, and 1/3 of patients require bed rest to manage the symptoms. The health-related impact on quality of life was comparable with that experienced by patients with congestive heart failure, hypertension, or diabetes.

While the burden of migraines on our society is clear, the pathophysiology of migraines remains largely unknown. The trigeminovascular system, including the external and internal carotid arteries and their associated sensory fibers which subserve the head have long been implicated in the pain and cutaneous allodynia experienced by migraine patients. Wolff in 1953, was the first to posit that migraine headache pain is the caused by dilation or circumferential expansion of the extracranial carotid artery. He demonstrated that migraineurs had twice the pulse amplitude in their external carotid arteries compared to control subjects and these changes were directly correlated to migraine symptoms. In a 2008 study, randomized migraineurs received nitroglycerin via peripheral IV or placebo for 20 minutes prior to obtaining magnetic resonance angiography (MRA). Nitroglycerin, a potent dilator of blood vessels, reliably induced migraine-like pain in up to 80% of patients, and transient dilation of vessels of up to nearly 40%, mostly in the extracranial vessels. Sumatriptan's efficacy in migraine relief provides further evidence for this theory, as it is a selective extracranial vessel constrictor which does not cross the blood brain barrier.

The goal of this current work is to utilize the direct, real-time angiography, which provides a high resolution map of vasculature, and demonstrate changes in vessel flow in patients who have migraine headache attacks. This information may guide therapeutic interventions in the future in order to better treat these migraine patients.


Condition or disease Intervention/treatment
Migraine Disorders Migraine, Classic Migraine Without Aura Drug: Nitroglycerin

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Understanding the Role of the External Carotid Artery in the Pathophysiology of Migraine Pain
Anticipated Study Start Date : October 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Migraine Intervention
Subjects who will be administered 200 micrograms of nitroglycerin once into branches of their external carotid artery to determine the role of dilation of this artery to cause migraine-like pain
Drug: Nitroglycerin
Intra-arterial adminstration to dilate external carotid artery branches and to replicate migraine pain
Other Name: Nitrostat


Outcome Measures

Primary Outcome Measures :
  1. Migraine [ Time Frame: 10 minutes ]
    The reporting of migraine-like pain after nitroglycerin administration


Secondary Outcome Measures :
  1. Migraine log pre-procedure: severity measure [ Time Frame: 2 weeks ]
    Severity of migraines for 2 weeks prior to angiogram

  2. Migraine log pre-procedure: frequency measure [ Time Frame: 2 weeks ]
    Frequency of migraines for 2 weeks prior to angiogram

  3. Migraine log pre-procedure: quality measure [ Time Frame: 2 weeks ]
    Quality of migraines for 2 weeks prior to angiogram

  4. Migraine log pre-procedure: location measure [ Time Frame: 2 weeks ]
    Location of migraines for 2 weeks prior to angiogram

  5. Migraine log pre-procedure: alleviating factor measure [ Time Frame: 2 weeks ]
    Alleviating factors of migraines for 2 weeks prior to angiogram

  6. Migraine log pre-procedure: aggravating factor measure [ Time Frame: 2 weeks ]
    Aggravating factors of migraines for 2 weeks prior to angiogram

  7. Migraine log pre-procedure: associated symptom measure [ Time Frame: 2 weeks ]
    Associated symptoms of migraines for 2 weeks prior to angiogram

  8. Migraine log pre-procedure: therapies utilized measure [ Time Frame: 2 weeks ]
    Therapies utilized for migraines for 2 weeks prior to angiogram

  9. Artery dilation [ Time Frame: 10 minutes ]
    Enlargement of the diameter of the vessel of interest after nitroglycerin administration

  10. Migraine pain relief [ Time Frame: 20 minutes ]
    Relief of induced migraine pain with temporary balloon occlusion of the dilated artery. Standard pain medication will also be available for treatment

  11. Adverse reactions [ Time Frame: 6 hours ]
    Monitoring for retroperitoneal hematoma, vascular injury, infection, contrast reaction, worsening contralateral headache symptoms, new neurologic deficit peri-procedurally until discharge

  12. Migraine log follow-up post-procedure: severity measure [ Time Frame: 2 weeks ]
    Severity of migraines for 2 weeks post-angiogram

  13. Migraine log follow-up post-procedure: frequency measure [ Time Frame: 2 weeks ]
    Frequency of migraines for 2 weeks post-angiogram

  14. Migraine log follow-up post-procedure: quality measure [ Time Frame: 2 weeks ]
    Quality of migraines for 2 weeks post-angiogram

  15. Migraine log follow-up post-procedure: location measure [ Time Frame: 2 weeks ]
    Location of migraines for 2 weeks post-angiogram

  16. Migraine log follow-up post-procedure: alleviating factors measure [ Time Frame: 2 weeks ]
    Alleviating factors of migraines for 2 weeks post-angiogram

  17. Migraine log follow-up post-procedure: aggravating factor measure [ Time Frame: 2 weeks ]
    Aggravating factors of migraines for 2 weeks post-angiogram

  18. Migraine log follow-up post-procedure: associated factor measure [ Time Frame: 2 weeks ]
    Associated symptoms of migraines for 2 weeks post-angiogram

  19. Migraine log follow-up post-procedure: therapies utilized measure [ Time Frame: 2 weeks ]
    Therapies utilized for 2 weeks after angiogram until follow-up clinic visit


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects with a documented diagnosis of migraine by a neurologist
  • Subjects refractory to standard migraine therapy with persistent severe, debilitating symptoms
  • Subjects without changes to their neurological exam within the preceding 6 months
  • Migraines at least twice a month
  • Migraines unique and distinguishable from other non-migraine headache pain
  • Subjects must sign a consent form for both angiography and for participation in this study, and must be willing to undergo angiography for the evaluation of their symptoms

Exclusion Criteria:

  • Subjects taking vasoactive drugs including epinephrine, norepinephrine, dopamine, dobutamine, isoprenaline, dopexamine, milrinone, amrinon, levosimendan, glucagon, phenylephrine, metaraminol, ephedrine, vasopressin, digoxin, and levothyroxine
  • Subjects with underlying cardiac pathology including but not limited to coronary artery disease, heart attacks, or severe atherosclerosis,
  • Subjects with severe pulmonary disease requiring supplemental oxygen therapy
  • Subjects taking medications similar to nitroglycerin such as phosphodiesterase inhibitors
  • Subjects with contraindications to nitroglycerin or calcium channel blocker use
  • Subjects who have had coffee, tea, or alcohol in the 12 hours before the start of the angiogram
  • Subjects having other headache conditions or pain syndromes
  • Subjects with prior intracranial therapies or craniotomies for management of any intracranial lesions
  • Subjects in whom the angiography demonstrates severe vessel tortuosity or stenosis, vasospasm not responsive to medical therapy, or abnormal communication between intracranial and extracranial vessels either in the past or during the study procedure
  • Subjects who are not able to reliably report symptoms
  • Subjects who do not consent to participate
  • Subjects who are pregnant and children
Contacts and Locations

Information from the National Library of Medicine

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): NCT03026101


Contacts
Contact: Andrew J Kobets, MD 7189207400 akobets@montefiore.org
Contact: David J Altschul, MD 7189207476 DAltschu@montefiore.org

Sponsors and Collaborators
Montefiore Medical Center
More Information

Publications:

Responsible Party: Andrew Kobets, Assistant Professor, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT03026101     History of Changes
Other Study ID Numbers: MontefioreMigraine
First Posted: January 20, 2017    Key Record Dates
Last Update Posted: August 30, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Migraine Disorders
Migraine without Aura
Migraine with Aura
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Nitroglycerin
Vasodilator Agents