Bilateral Middle Meningeal Artery Lidocaine Infusion for Chronic Debilitating Migraines

Given the current literature and using intent-to-treat clinical judgement, the research team believes that the treatment offered in this study may offer a promising benefit to treatment resistant migraine patients. Despite modest advances in drug therapy, some patients still suffer from chronic migraines. Therefore, the headache medicine community continues to search for alternative treatments in the form of research.

The research team is conducting a prospective observational study to gather data before and after this treatment is administered to determine whether there is improvement in migraine duration, intensity, and frequency.

This treatment is an intra-arterial bilateral lidocaine infusion into the middle meningeal artery (i.e. this is a lidocaine infusion into the brain blood vessels to turn off the pain receptors responsible for causing chronic headaches).

Lidocaine is an FDA approved anesthetic (i.e. pain killer) used in common medical practice. Lidocaine, however, has not yet been approved by the FDA for this particular use. For this reason, the use of lidocaine in this study is considered investigational.

This is NOT the first time this procedure has been performed. Intra-arterial lidocaine infusion has been used safely during the treatment of other brain diseases. Infusing brain vessels with lidocaine is not new technique. The treatment offered in this study is new for the treatment of migraines. This particular treatment has been performed successfully in the small group studies that the study investigators are modeling after. The investigative neuro-interventionists have been rigorously trained for this approach and hold a minimum of double board certifications. This team is experienced in using these techniques for other brain diseases and have successfully performed this specific procedure in a select group of early patients. Collectively, the team holds over 45+ years of experience in performing neuro-endovascular procedures.

During the intra-arterial infusion of lidocaine for treatment of a subdural procedure, an incidental finding noted that patients had reduced headache intensity following this treatment.

Therefore, this technique has been re-purposed in this study to treat chronic migraine sufferers. The procedure is considered investigational because lidocaine is not yet FDA-approved for this specific use. Although several studies have demonstrated that this approach is a safe and tolerable treatment for chronic migraine, there is still insufficient evidence to incorporate it into the current day standard of care protocol.

Ultimately, the purpose of this study is to explore this approach to and determine if this treatment can induce a significant improvement in chronic migraine, intensity, duration, and frequency.

Inclusion criteria

• Adults aged 18 to 75 years with a very severe to extremely severe medically refractory Chronic Daily Headache (CDH).

• Chronic: as defined by the International Headache Society Classification ICHD 3 (>15 headache days a month for a period of at least 3 months)
• Medically refractory: defined as failure of ≥3 headache preventative treatments.
• Severely disabling (Migraine Disability Assessment [MIDAS] Tool score of ≥ 21 [Grade IV])
• Score of 6 (very severe) or 7 (extremely severe) on the Global Assessment of Migraine Severity (GAMS) rating scale.
• Head pain is at least moderate-to-severe intensity (>5 on a Visual Analog Scale) in ≥50% of headaches.
• Diagnosis of CDH for ≥ 12 months before screening based on medical records and/or patient self-report.
• Headache frequency: minimum 15 monthly headache days (MHD) on average across the 3 months prior to screening
• Patient reports to their provider intolerance or insufficient response with their current preventive treatment (i.e. insufficient reduction in headache frequency, duration, and severity on a standard treatment on a generally accept therapeutic dose for 6 weeks).
• On a stable concomitant medication and headache preventive for the 3 months prior to screening

During Baseline Period:

• Must have ≥ 15 MHD based on the patient self-maintained diary data during the baseline period.
• Must have demonstrated >75% compliance with diary data for the 28 day duration period, or longer if their baseline period carries on past this point.
• Must continue to meet eligibility criteria when reassessed at baseline completion visit

Exclusion criteria

• Recently started new migraine preventative treatment regimen within the past 3 months.
• Known allergy or sensitivity to lidocaine.
• Lidoderm patch (not an exclusion if the Lidoderm patch has been removed for ≥ 3 days before the procedure)
• Severe allergy/anaphylaxis to iodinated contrast dye.
• Any intracranial pathology on brain imaging (head CT or MRI within the past 12 months)
• Chronic subdural hematoma
• Ischemic stroke or myocardial infarction within 3 months 8. History of renal insufficiency with Cr > 1.5 within 3 months (will be retested during pre-surgical

testing).

• History of abnormal ECGs within 3 months, specifically:

• Prolonged QT syndrome
• Use of medications that may prolong the QT interval such as: anti-nausea, anti-emetics, etc.

• Taking any antiarrhythmic medication (other than a beta blocker)

• Symptomatic peripheral arterial disease

• Known inherited or acquired bleeding diathesis (not including antiplatelet or anticoagulation medication)

• Evidence of active substance-related disorders, addictive disorders, or "recreational use" of illicit drugs.

a. If any of these disorders have occurred within 12 months prior to screening, based on medical records, patient self-report, or positive urine drug test (except for prescribed medications that may result in a positive urine drug test).

• Active chronic pain syndromes (e.g., fibromyalgia and chronic pelvic pain).

• History of major psychiatric disorder or current evidence of moderately severe or severe depression based on a Patient Health Questionnaire-9 (PHQ-9) total score ≥ 15 at screening.

a. Subjects with history of anxiety disorder and/or major depressive disorder with PHQ-9 < 15) and are taking no more than 1 medication, for each disorder, for at least 2 months prior to screening may be considered.

• If the subject is pregnant, planning on pregnancy during the duration of the study, or planning on making their partner pregnant will be excluded from the study unless proper contraception is in place.

• Any diagnosis at the discretion of the investigator that would make the patient unfit.