A Study Investigating Peripheral Cryoneurolysis in Adults With Chronic Migraine

Inclusion Criteria:

1. Participant must be 18 years at the time of signing the informed consent

2. Migraine, with or without aura, fulfilling the International Classification ofHeadache Disorders (ICHD) III criteria 1.3. for chronic migraine at time ofinclusion, verified by a neurologist

3. History of 8 debilitating headache days per month for at least 3 consecutive months.Debilitating headache is defined as headache causing serious impairment to conductactivities of daily living despite the use of pain-relief drugs with establishedefficacy at the recommended dose and taken early during the attack; failure of atleast two different triptans is required.

4. Chronic migraine at least for a period of 1 year prior to inclusion

5. Debut of episodic migraine before the age of 50, and chronic migraine before the ageof 65.

6. The condition is pharmacologically resistant as defined in EHF guidelines as lack ofefficacy, lack of tolerability and/or contraindications to at least 3 of thefollowing drug classes

7. Antidepressant (Amitryptyline, Venlafaxine)

8. Antiepileptic (Topiramate or Valproate)

9. Beta-blocker (Atenol, Metropolol, Propanolol, Timolol)

10. Calcium channel blockers (Flunarizine or Cinnarizine)

11. Drugs acting on the CGRP pathway (Monoclonal antibodies and gepants)

12. Angiotensin-converting enzyme inhibitors (Lisinopril) or angiotensin IIreceptor blocker (Candesartan)

13. OnabotulinumtoxinA

14. Subject has had no change in type, dosage or dose frequency of preventive headachemedications < 3 months prior to baseline/screening, or a minimum of 5 half-lives,whichever is longer.

15. Subjects has not been treated with steroids orally or injections >8 weeks (excludingsteroid inhalations or topical treatments) prior to baseline and agrees to refrainfrom steroids orally or injections during baseline and 8 weeks post-intervention.

16. Subject agrees to maintain current preventive headache medication regimens (nochange in type, frequency, or dose) during baseline and 8 weeks after theintervention.

17. Be an appropriate candidate for the study intervention required in this study on thebasis of the clinical judgment of the investigator

18. Capable of giving signed informed consent as which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

Exclusion Criteria:

1. Subject is unable to differentiate migraine from other concomitant headaches.

2. Subject with secondary headache conditions, with the exception of medication overuseheadache.

3. Subject that, in the opinion of the investigator, has had no or minimal response tomore than 6 adequate trials of prophylactic migraine treatment of the following drugclasses:

4. Antidepressant (Amitryptyline, Venlafaxine)

5. Antiepileptic (Topiramate or Valproate)

6. Beta-blocker (Atenol, Metropolol, Propanolol, Timolol)

7. Calcium channel blockers (Flunarizine or Cinnarizine)

8. Drugs acting on the CGRP pathway (Monoclonal antibodies and gepants)

9. Angiotensin-converting enzyme inhibitors (Lisinopril) or angiotensin IIreceptor blocker (Candesartan)

10. OnabotulinumtoxinA

11. Subject has had a change in type, dosage or dose frequency of preventive headachemedications during the baseline period.

12. Ongoing abuse of drugs (including narcotics) or alcohol.

13. More than 4 days of opioid use per month (including codeine and tramadol), and anyuse of barbiturates

14. Other pain conditions, not intended to be treated in this study, that in the opinionof the investigator could interfere with study procedures, accurate pain reporting,and/or confound evaluation of study endpoints.

15. High probability of deterioration due to other medical conditions, that in theopinion of the investigator may confound outcome assessment.

16. Other coexisting current medical conditions, including, but not limited to, bleedingdiathesis and thrombophilia, that presents excess procedural risk, in the opinion ofthe investigator.

17. Abnormal pain behavior, inappropriate medication use and/or unresolved psychiatricillness, that in the opinion of the investigator are significant enough to impactperception of pain, compliance with intervention and/or ability to evaluatetreatment outcome.

18. Anomaly or trauma which renders the planned procedure difficult.

19. Subject currently has an active abscess or a local infection at the site ofintervention based on present symptoms.

20. Subject has been diagnosed with any major infectious processes such asosteomyelitis, or primary or secondary malignancies involving skull or site ofintervention that have been active or required treatment in the past 6 months.

21. Patients with any kind of conductive implant with contraindication for nervestimulation.

22. The subject is not competent to consent