Study of the Effectiveness and Safety of Embolization of the Middle Meningeal Artery Using Non-adhesive Materials SQUID 12 and SQUID 18 in the Treatment of Patients with Chronic Resistant Migraine

Inclusion Criteria:

1. The patient has read, understood, signed, and dated the Patient Information Sheetwith the informed consent form.

2. The patient is aged between 35 and 59 years inclusive at the time of signing thePatient Information Sheet with the informed consent form.

3. The diagnosis of "chronic migraine" according to the clinical guidelines on migraineby the Ministry of Health of the Russian Federation (2021) / ICD-10 (2018),established at least 12 months before screening.

4. Resistant nature of the migraine, determined by the doctor using the criteria of theEuropean Headache Federation (EHF, 2020), established at least 6 months beforescreening.

5. At least 14 days of headache during the screening period (28 days), of which 8 daysof headache meet the definition of migraine (assessed based on the results offilling out the Headache Diary for 28 days during the screening period).

6. Migraine, resistant to both pharmacological and non-pharmacological prevention andtreatment methods, in the patient's history.

7. Maximum level of headache during migraine days above 5 points (inclusive) on a 10-point numerical rating scale during the screening period.

8. No positive effect on migraine symptoms (frequency and intensity of headacheattacks) from previous botulinum toxin therapy (administration ofOnabotulinumtoxinA, Relatox® (botulinum toxin type A - hemagglutinin complex 155 - 195 IU, administered every 12 weeks according to the PREEMPT protocol).

9. Consent to use adequate contraceptive methods* and not serve as an egg/sperm donorfrom the time of signing the Patient Information Sheet with the informed consentform for participation in the study until the end of the study (for women withreproductive potential and men).

Exclusion Criteria:

1. The patient has contraindications to undergoing embolization of the middle meningealartery based on the medical history, results of examinations, and laboratory testsconducted during screening.

2. Allergic reactions to contrast agents used during procedures before/during theembolization procedure and associated procedures.

3. The patient has a history of cerebral vascular malformations, arteriovenousmalformations, brain aneurysms, brain tumors, hydrocephalus, arachnoiditis,cerebrospinal fluid circulation disorders, craniovertebral junction anomalies,platybasia, skull base deformities, severe traumatic brain injuries, stenosis, andocclusion of pre-cerebral arteries.

4. The patient has a history of skull base fractures and consequences of skull basefractures, history of neurosurgical operations.

5. A history of mental illness (including depression, confirmed by a psychiatristduring screening through the HADS questionnaire and Hamilton scale assessment),which, in the opinion of the psychiatrist, may affect the patient's ability toassess their condition, interfere with participation in the study, or impact thepatient's safety during the study.

6. A history of hyperthyroidism or diabetes. The presence of other endocrine disordersin the patient's history that, in the doctor's opinion, could interfere withparticipation in the study or affect the evaluation of efficacy and/or safety.

7. History or data of drug addiction, alcoholism, or abuse of medications.

8. Medication-induced headache at the time of screening and within 3 months (12 weeks)prior to screening.

9. Other types of chronic headache in the patient's history within less than 12 monthsbefore screening, such as trigeminal autonomic cephalalgias (including clusterheadaches, prolonged hemicrania), new daily persistent headaches, painful cranialneuropathies, retinal migraine, aura without headache, hemiplegic migraine,brainstem aura migraine, idiopathic intracranial hypertension without optic nerveedema, spontaneous intracranial hypertension, secondary headaches.

10. The patient is unable to distinguish a migraine headache from other types ofheadache.

11. The patient has migraine complications, such as status migrainosus, persistent aurawithout infarction, migraine infarction, migraine aura (as a trigger for epilepticseizures).

12. Body mass index (BMI) below 18.5 or above 39.9 kg/m².

13. The onset of migraine was diagnosed at an age older than 50 years.

14. The presence of metabolic syndrome or cachexia.

15. Severe cardiovascular diseases currently or in the past, including: chronic heartfailure class III or IV (according to the New York Heart Associationclassification), clinically significant ventricular arrhythmias (ventriculartachycardia, ventricular fibrillation), significant heart valve diseases,uncontrolled hypertension with systolic blood pressure > 180 mm Hg and diastolicblood pressure > 110 mm Hg, pulmonary embolism, or deep vein thrombosis.

16. Varicose veins of the lower limbs, history of lower limb vein thrombosis.

17. Ischemic heart disease, atherosclerosis of coronary vessels.

18. Stenotic atherosclerosis of brachiocephalic arteries in the patient's history.

19. Acute cerebrovascular accident or its consequences in the patient's history.

20. The patient is pregnant or plans to become pregnant within the next 3 months.

21. Atrial fibrillation, patent foramen ovale, anomalies of the interatrial septum,history of heart and coronary vessel surgeries.

22. Signs of blood clotting disorders in the patient's history and screening, history ofantiphospholipid syndrome.

23. Use of anticoagulant drugs less than 5 days before the procedure.

24. Uncontrolled bronchial asthma, severe chronic obstructive pulmonary disease in thepatient's history.

25. Renal insufficiency at screening based on the calculation of glomerular filtrationrate (GFR) ≤ 60 mL/min, based on serum creatinine levels at screening, or a historyof renal insufficiency.

26. History of liver insufficiency, elevated ALT and AST levels at screening.

27. History of generalized pain syndrome, fibromyalgia.

28. For women: use of combined oral contraceptives with a history of thrombosis of anylocalization.

29. History of epilepsy, epileptic syndrome, seizure disorders, neurological conditionsother than the primary condition (migraine).

30. Presence of antibodies to HIV, hepatitis C virus, hepatitis B surface antigen (HbsAg), antibodies to T. Pallidum, or a history of HIV infection, hepatitis B,hepatitis C, or syphilis, either in the medical history or based on the results ofserological blood tests at screening.

31. Malignant neoplasms within 5 years before screening, or current or suspectedoncological disease.

32. Other serious, unstable, decompensated, or clinically significant medical orpsychological conditions that, in the opinion of the doctor, may interfere with thepatient's participation in the study or affect the evaluation of efficacy and/orsafety.

33. Participation in other interventional clinical trials, including the studycompletion visit, within 30 days prior to the screening, or planning to participatein such studies during the current study. Participation in non-interventionalregistry or epidemiological studies is allowed.

34. The patient is unable to read or write, unwilling or unable to comply with the studyprotocol procedures; any other conditions that, in the opinion of the doctor, mayprevent participation in the study, adherence to procedures, or contradict thepatient's interests, as well as affect the study results.

35. Employees of the medical institution conducting the study or the sponsor company,their family members, or subjects in dependent relationships.