Bilateral Embolization of the Middle Meningeal Arteries for Refractory Chronic Migraine (MMAE-Migraine)

A Pilot Study of Safety and Feasibility of Bilateral Middle Meningeal Artery Embolization (bMMAE) in Patients With Refractory Chronic Migraine Headache: The MMAE-MIGRAINE Trial

This study is to test the safety and feasibility of a procedure called embolization of the middle meningeal arteries (MMA), using a product called Onyx. Embolization creates a plug in the arteries. MMA embolization with Onyx is not approved for use in patients with migraines, but is currently used in patients with subdural hematomas. The FDA is allowing the use of Onyx in this study. It is thought that by using Onyx to block the middle meningeal arteries, the amount of migraine-causing substances which are released into the brain's bloodstream will be reduced. The company that manufactures Onyx, Medtronic, is providing the supplies for this study.

Participants will be in the study for about 8 months after enrolling, including 6 months of follow up after the procedure. The participants will be asked to complete a daily headache diary and continue the participant's regular migraine medications. Participants will also have several clinic visits and be asked to provide blood samples for research.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Chronic Migraine Headache; Refractory Migraine
• Intervention / Treatment: Device: embolization of middle meningeal arteries

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kelly Szajna; Phone Number: 000-000-0000; Email: ksajna1@jhmi.edu
• Study Contact Backup: Name: Kallan Dirmeyer; Phone Number: 000-000-0000; Email: kdirmey1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Medicine
      • Principal Investigator: Risheng Xu, MD, PhD
      • Contact: Kelly Szajna; Phone Number: 000-000-0000; Email: kszajna1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age 18<x<80
• Meets ICHD3 criteria for chronic migraine, (ICHD3, 1.3; with inclusion of ICHD3 1.1 and 1.2.1 only), with first migraine before age 50 (in concordance with previously published trials in migraine therapy36,39) . Patients must experience bilateral migraine symptoms.
• Satisfy criteria for refractory chronic migraine defined as failure of, inadequate response to, or inability to tolerate migraine preventatives in at least 2 classes. Migraine preventatives include beta-blockers, calcium channel blockers, anti-convulsants (valproic acid, topiramate), anti-depressants (venlafaxine, amitriptyline), CGRP monoclonal antibodies, botulinum toxin injections. Chronic migraines must have persisted for at least 12 months prior to enrollment and at least 6 months after failing 2 classes of medication.
• Has not used opiates or barbiturates as acute (rescue) therapy for migraine headache. Opiate or barbiturate use for reasons other than migraine is allowed. Other classes of acute migraine medications are acceptable. Acute (rescue, abortive) medications for migraines include acetaminophen, NSAIDs (ibuprofen, naproxen), gepants, triptans, anti-emetics (anti-nausea medications).
• Exclusion of secondary headache disorder which may cause migraines/symptoms, including MRI/MRA (performed as routine care showing no underlying lesion that may be causing headaches, within 3 years of screening).
• At least one migraine free day during the last month per headache diary.
• Minimum MIDAS score of 21 (reflecting severely disabling migraine, in concordance with ongoing MMA lidocaine infusion trial44).
• Able to read/write in English. Patients who are not English language users will not be enrolled as the study assessments are only validated in English.
• Able to sign informed consent for themselves.
• Able to complete study requirements/follow-up as outlined in study plan section 3.6.

Exclusion criteria:

• History of cranial or cervical vascular interventions or surgery, including craniotomy/craniectomy, shunt placement, stereoelectroencephalography, and carotid endarterectomy.
• A history of opiate or barbiturate use for the treatment of chronic migraine within one year.
• Current intracranial lesions as determined by routine care MRI for exclusion of secondary headache disorders.
• History of cranial radiation treatment.
• Patients with additional diagnoses under ICHD3 (such as hemiplegic migraine, basilar migraine, new daily persistent headache, or cluster headache) are ineligible
• Significant liver function impairment or serum creatinine > 2.0 mg/dL. Patients with elevated creatinine levels who are on dialysis may be eligible.
• History of systemic malignancy or auto-immune inflammatory disorders (such as multiple sclerosis, rheumatoid arthritis, autoimmune diseases).
• History of life-threatening allergy to radiographic contrast. Patients with this allergy may be eligible if it can be managed medically.
• Enrollment in another migraine study which could confound this study's endpoints, including undergoing any intervention or receiving an experimental drug under investigation for migraine therapy.
• Additional medical or social concerns which could confound this study's endpoints or otherwise create undue risk or interfere with the participant's ability to complete the study, as assessed by the PI.
• As this study is open only to patients with chronic migraine, which is refractory to treatment, patients who have previously been diagnosed with chronic migraine but now experience episodic migraine due to effective therapy are not eligible.
• Patients with additional diagnoses under ICHD3 (such as hemiplegic migraine, basilar migraine, new daily persistent headache, or cluster headache) are ineligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Participants will undergo embolization of the middle meningeal arteries with Onyx.	Device: embolization of middle meningeal arteries; Participants will undergo embolization of the middle meningeal arteries with Onyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of specified adverse events related to the study	Strokes (ischemic and hemorrhagic), blindness, facial palsy, epidural hematoma, and death within 30 days of the embolization	30 days after procedure

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Medtronic
• Investigators: Principal Investigator: Risheng Xu, MD, PhD, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: October 28, 2025
• First Posted (Actual): October 31, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: embolization; middle meningeal artery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: IRB00513681

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes