Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Migraine

Exclusion Criteria

• •1. Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
• •2. Subject is unable to differentiate migraine from other concomitant headaches.
• •3. Subject with secondary headache conditions, with the exception of medication overuse headache.
• •4. Non-responder in regular clinical practice to preventive medications from ≥6 of the following 7 drug classes:
• •1. Beta-blockers
• •2. RA(A)S-inhibitors
• •3. Calcium-antagonists
• •4. Antiepileptic drugs
• •5. Tricyclic antidepressants
• •6. Botulinum toxin A
• •7. CGRP antagonists
• •5. Subject has had a change in type, dosage or dose frequency of preventive headache medications \< 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
• •6. Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration
• •7. Botulinum toxin injections in the head and neck region, as part of migraine treatment or otherwise indicated on medical or cosmetic grounds, in the last 4 months before inclusion.
• •8. The discontinuation of CGRP-antagonists within 3 months before study inclusion or 5 half-lives, whichever is longer,
• •9. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion or 5 half-lives, whichever is longer.
• •10. Subject is currently participating or has participated in the last 3 months in another clinical study in which the subject has, is, or will be exposed to an investigational or non-investigational drug or device.
• •11. Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the trigeminal ganglion or any branch of the trigeminal nerve.
• •12. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the SPG.
• •13. Subject has had blocks of short-acting anaesthetics of the SPG in the last 3 months.
• •14. Subject is or has been treated with occipital nerve stimulation or deep brain stimulation.
• •15. Ongoing abuse of drugs (including narcotics) or alcohol.
• •16. More than 4 days of opioid use per month (including codeine and tramadol), and any use of barbiturates
• •17. Treatment with pharmacological substances prior to SPG-injection that may interact with BTA (aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), and anticholinesterases).
• •18. Inadequate contraceptive use. Women of childbearing potential (WOCBP) who do not use highly effective contraception (HEC) or use other medication that may interact and/or otherwise reduce the efficacy of the contraceptive agents in use.
• •19. Subject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary at the planned injection site that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
• •20. Facial anomaly or trauma which renders the procedure difficult.
• •21. Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
• •22. Subject has been diagnosed with any major infectious processes such as osteomyelitis, or primary or secondary malignancies involving the face that have been active or required treatment in the past 6 months.
• •23. Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator
• •24. Patients exhibiting a high degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator
• •25. Patients with disorders that severely inhibits lacrimation, at the discretion of the investigator
• •26. Patients with previous ischemic cardiovascular and cerebrovascular disorder with, in the opinion of the investigator, a moderate to high risk of new ischemic episodes.
• •27. Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
• •28. Subject has a history of bleeding disorders or coagulopathy, that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
• •29. Unable to stop antithrombotic medication e.g. platelet aggregation inhibitors and/or anticoagulation therapy, prior to procedure.
• •30. The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:
• •* mentally or legally incapacitated or unable to give consent for any reason
• •* in custody due to an administrative or a legal decision, under tutelage, or being admitted to a sanatorium or social institution
• •* has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study
• •31. The patient is a study centre employee who is directly involved in the study or the relative of such an employee.