Understanding the Pathophysiology of Migraine Pain

NCT03026101 | Terminated DMC

• 1 other identifier: 2017-8335
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine Disorders; Migraine, Classic; Migraine Without Aura

Outcome Measures

Primary Outcomes (1)

• Migraine

  The reporting of migraine-like pain after nitroglycerin administration

  10 minutes

Secondary Outcomes (19)

• Migraine log pre-procedure: severity measure

  2 weeks

• Migraine log pre-procedure: frequency measure

  2 weeks

• Migraine log pre-procedure: quality measure

  2 weeks

• Migraine log pre-procedure: location measure

  2 weeks

• Migraine log pre-procedure: alleviating factor measure

  2 weeks

Study Arms (1)

Migraine Intervention

EXPERIMENTAL

A catheter will be placed in the symptomatic side external carotid artery and a diagnostic angiogram will be performed. The diameter of the occipital artery, superficial temporal artery and middle meningeal artery will be measured. Depending on the location of the headache superselective catheterization with microcatheter will be placed in either superficial temporal artery, occipital artery or middle meningeal artery. A volume of 50µg of nitroglycerin diluted in 10ml saline will be injected into the branch of interest dependent on laterality and location of symptoms over 30 seconds, to be delivered into these vessels only. 1 minute after superselective nitroglycerin injection the patient will be questioned as to whether the headache has been induced. A follow up diagnostic angiogram of the external carotid artery will be performed 3 minutes after injection. If there is no response to the lower 50µg, a dose of 150µg nitroglycerin in 10ml saline will be administered.

Other: Nitroglycerin

Interventions

Nitroglycerin OTHER

Intra-arterial adminstration to dilate external carotid artery branches to replicate migraine pain

Also known as: Nitrostat

Migraine Intervention

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• No changes to neurological exam within the preceding 6 months
• Requirement of a diagnostic cerebral angiogram for a previously treated aneurysm or arteriovenous malformation with no history of persistent disease
• A documented diagnosis of migraine made by a neurologist
• Migraines that are refractory to standard migraine pharmacologic treatment, with or without aura, either prophylactic or abortive, with persistent severe, debilitating symptoms
• Experience migraine symptoms at least twice a month
• Migraines symptomology which is discernible 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

You may not qualify if:

• Patients with persistent intracranial vascular anomalies, such as aneurysms, which remain untreated, in whole or in part
• Patients taking vasoactive drugs including epinephrine, norepinephrine, dopamine, dobutamine, isoprenaline, dopexamine, milrinone, amrinon, levosimendan, glucagon, phenylephrine, metaraminol, ephedrine, vasopressin, digoxin, and levothyroxine
• Patients with underlying cardiac pathology including but not limited to coronary artery disease, heart attacks, or severe atherosclerosis
• Patients taking medications such as phosphodiesterase 5 (PDE5) inhibitors or other nitroglycerin analogues
• Patients with pulmonary disease requiring supplemental oxygen therapy
• Patients with contraindications to nitroglycerin or calcium channel blocker use
• Patients who have had coffee, tea, or alcohol in the 12 hours before the start of the angiogram
• Patients having other headache conditions, pain syndromes, or prior intracranial therapies or craniotomies for management of any vascular lesions that would require angiography for surveillance and confound their evaluation of their migraine pain
• Patients in whom the angiography demonstrates the anatomy is not appropriate for endovascular treatment, due to conditions such as:
• Severe vessel tortuosity or stenosis
• Vasospasm not responsive to medical therapy
• Abnormal communication between intracranial and extracranial vessels either in the past or during the study procedure
• Patients who are not able to reliably report symptoms
• Patients without the capacity to consent
• Patients who do not consent to participate

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (38)

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MeSH Terms

Conditions

Migraine Disorders; Migraine with Aura; Migraine without Aura

Interventions

Nitroglycerin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals

Study Officials

• David J Altschul, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: January 20, 2017
• Study Start: January 1, 2017
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)